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Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle: Daily muscle stretching and blood flow
Abstract
Key points:
In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise.
Abstract:
Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day-1, 5 days week-1, for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.
... 8 Our recent work in aged rats that indicates static muscle stretching, when performed regularly for 4 wk, increases muscle blood flow during exercise, enhances endothelium-dependent vasodilation of skeletal muscle resistance arteries, and induces angiogenesis in stretched muscles. 9 In addition, expression of endothelial nitric oxide synthase increased in resistance arterioles of stretched muscle and expression of vascular endothelial growth factor (VEGF) increased in stretched muscle fibers. During the development of the mammalian skeletal system, bone formation is tightly coupled to angiogenic growth of blood vessels 3,10,11 and VEGF-A has been shown to be a significant regulator of blood vessel invasion, cartilage remodeling, and growth plate morphogenesis. ...
... To identify the vascular endothelium, sections were washed with PBS, and incubated with rhodamine-labeled Griffonia Simplicifolia lectin I (15 μg/mL diluted with PBS, VECTOR LABORA-TORIES) for 30 min at room temperature in the dark. 9,22 Sections were visualized with a fluorescence microscope and images were captured with a digital CCD camera (6.3X magnification). To confirm that lectin was binding specifically to the endothelium, staining was also performed using a primary anti-VEGFR2 (vascular endothelial growth factor receptor 2) and a secondary FITC-labeled anti-IgG. ...
... Body weights and tibia weights did not differ between naive rats and rats that underwent sham stretching. 9 Tibia weights from the stretched limbs were significantly higher than those from the nonstretched limbs (841 ± 15 mg vs 815 ± 18 mg; stretched vs non-stretched, P < .001). Tibia weight/body weight was also higher for the stretched limbs as compared with the nonstretched limbs (2.08 ± 0.05 mg/g vs 2.14 ± 0.04 mg/g; stretched vs non-stretched, P < .001). ...
The magnitude of bone formation and remodeling is linked to both the magnitude of strain placed on the bone and the perfusion of bone. It was previously reported that an increase in bone perfusion and bone density occurs in the femur of old rats with moderate aerobic exercise training. This study determined the acute and chronic effects of static muscle stretching on bone blood flow and remodeling. Old male Fischer 344 rats were randomized to either a naïve or stretch-trained group. Static stretching of ankle flexor muscles was achieved by placement of a dorsiflexion splint on the left ankle for 30 min/day, 5d/wk for 4wks. The opposite hindlimb served as a contralateral control (nonstretched) limb. Bone blood flow was assessed during and after acute stretching in naïve rats, and at rest and during exercise in stretch-trained rats. Vascular reactivity of the nutrient artery of the proximal tibia was also assessed in stretch-trained rats. MicroCT analysis was used to assess bone volume and micro-architecture of the trabecular bone of both tibias near that growth plate. In naïve rats, static stretching increased blood flow to the proximal tibial metaphasis. Blood flow to the proximal tibial metaphysis during treadmill exercise was higher in the stretched limb after 4 weeks of daily stretching. Daily stretching also increased tibial bone weight and increased total volume in both the proximal and distal tibial metaphyses. In the trabecular bone immediately below the proximal tibial growth plate, total volume and bone volume increased, but bone volume/total volume was unchanged and trabecular connectivity decreased. In contrast, intravascular volume increased in this region of the bone. These data suggest that blood flow to the tibia increases during bouts of static stretching of the hindlimb muscles, and that 4 weeks of daily muscle stretching leads to bone remodeling and an increase in intravascular volume of the tibial bone.
... However, to the best of our knowledge, no studies have examined the hemodynamic effects of multifunctional training associated with flexibility training in older women with SAH. In flexibility training, responses to mechanical stretch and shear stimuli improve muscles and tendons (mechanical shear stress of muscles and tendons), and also have effects on target muscle vasculature, which is important for maintaining vascular function (Hotta et al., 2018;Pepera et al., 2021). ...
... Although the beneficial effects of exercise are known, the rate of adherence to physical training programs is low in people with special conditions (Hotta et al., 2018). Older people and people with obesity may have physical or musculoskeletal limitations, which can reduce their participation in more active or strenuous modalities or in conventional places of physical exercise. ...
... The intensity of muscle stretching exercise is relatively light compared to aerobic exercise, so that even the oldest old and/or obese individuals can perform muscle stretching exercise with minimal risk of injury (Lima et al., 2017). Improvements in health parameters, such as hemodynamics, are seen in the literature, separately for flexibility training (through active stretching exercises) and other types of training (Lima et al., 2017;Hotta et al., 2018;Bisconti et al., 2020). Flexibility training through stretching exercises is feasible for these individuals due to its greater safety and clinically relevant reported results (Bisconti et al., 2020). ...
Background: Body relaxation and pain reduction are some of the reported benefits of flexibility training (through active stretching exercises), however their effects on posture and blood circulation are uncertain. We aimed to investigate the effects of flexibility training (through active stretching exercises) in combination with multicomponent training (MT) on blood pressure (BP), and the correlation with changes in body alignment and flexibility in physically inactive women.
Methods: Women aged 60–70 years were into three groups: multicomponent training group (MT), multicomponent training plus flexibility training group (FT), and control group (CG). After randomization, the resting blood pressure was measured and the participants were reallocated into subgroups according to pressure values >130/80 mmHg (This classification is according to the American Heart Association (AHA), resulting in the subgroups: flexibility training (FT); flexibility training for hypertensive patients (FTSAH); multicomponent training (MT); multicomponent training for hypertensive patients (MTSAH); control group (CG); control group of hypertensive patients (CGSAH). The interventions lasted 14 weeks. Systolic (sBP) and diastolic (dBP) BP, range of motion (flexion and extension), and postural analysis by asymmetry in the frontal plane and asymmetry in the sagittal plane, displacement and the flexibility test were collected before (Pre) and after training (Post). In total, 141 women participated in the study (without SAH: FT = 23, MT = 20, and CG = 21; with SAH: FTSAH = 28, MTSAH = 23, and CGSAH = 26).
Results: Systolic blood pressure, in the pre and post moments were: FT (116 ± 6.7 vs. 114 ± 4.7); FTSAH (144 ± 16.5 vs. 121 ± 10.1); MT: (120 ± 6.8 vs. 121 ± 7.3); MTSAH: (137 ± 10.6 vs. 126 ± 13.0); CG: (122 ± 5.3 vs. 133 ± 19.2); and CGSAH: (140 ± 9.7 vs. 143 ± 26.2), presenting an F value (p-value - group x time) of 12.00 (<0.001), with improvement in the groups who trained. The diastolic blood pressure in the pre and post moments were: FT (71 ± 4.7 vs. 74 ± 6.8); FTSAH (88 ± 9.6 vs. 70 ± 12.0); MT: (74 ± 4.5 vs. 77 ± 11.7); MTSAH: (76 ± 10.4 vs. 76 ± 10.2); CG: (69 ± 7.11 vs. 82 ± 11.4); and CGSAH: (76 ± 13.4 vs. 86.6 ± 7.7), presenting an F value (p-value - group x time) of 8.00 (p < 0.001), with improvement in the groups who trained. In the Elastic Net Regression, sBP was influenced by height (β: −0.044); hip flexion (β: 0.071); Shoulder extension (β: 0.104); low back flexion (β: 0.119) and dBP (β: 0.115). In the Elastic Net Regression, dBP was influenced by asymmetry in the sagittal plane variables (0.040); asymmetry in the frontal plane (β: 0.007); knee flexion (β: −0.398); BM (β: 0.007); Shoulder flexion (β: −0.142); Hip flexion (β: −0.004); sBP (β: 0.155) and Ankle Flexion (β: −0.001).
Conclusion: The displacement of the asymmetry in the frontal plane and asymmetry in the sagittal plane, and the increase in the flexion position in the hip, lumbar, head, and knee regions, influenced the highest-pressure levels. Multicomponent training associated with flexibility training promoted improvement in body alignment, COM, and joint angles, and decreased blood pressure.
... Additionally, it has been noted that passive movement of the lower limbs in young people increases blood flow and VEGF levels in the muscles, producing results similar to those of exercise (60)(61)(62). This suggests that passive muscle stretching is a sufficient mechanical factor to initiate angiogenesis in skeletal muscles (63). Massage is an example of such an action. ...
... Roseguini et al. showed in animal studies that changes in VEGF expression were evident in the group where a highfrequency mechanical stimulus (compression) was applied (66). Such a mechanism of massage was confirmed by Hotta et al. (63). While investigating the role of the endothelium in skeletal muscle, Hotta et al. showed that extracellular mechanical stimuli, such as shear and tensile stresses, induced biochemical reactions inside vascular endothelial cells, thus stimulating the initiation of angiogenesis (63). ...
... Such a mechanism of massage was confirmed by Hotta et al. (63). While investigating the role of the endothelium in skeletal muscle, Hotta et al. showed that extracellular mechanical stimuli, such as shear and tensile stresses, induced biochemical reactions inside vascular endothelial cells, thus stimulating the initiation of angiogenesis (63). ...
Background/aim:
Angiogenesis induced in muscles or massaged tissue is thought to support their regeneration and performance. Therefore, different methods that could promote angiogenesis are investigated. The aim of this study was to examine whether the use of the foam roller massager for lower limb muscles affects VEGF-A and FGF-2 levels in young men.
Materials and methods:
The study group included 60 healthy young men attending Military University of Land Forces, Wroclaw, Poland. The participants were randomly divided into two groups. The experimental group included 40 individuals who performed self-massage of the lower limbs using a foam roller. The control group comprised 20 individuals who did not perform massage. Massage was applied to lower limb muscles four times a week for seven weeks. Blood was collected before the experiment and after weeks 1, 3, 5, and 7. ELISA was used to determine changes in VEGF-A and FGF-2 levels in blood serum.
Results:
The results of the study demonstrated a significant increase in VEGF-A serum levels in the group of individuals who underwent massage each week compared to VEGF-A concentrations before the experiment. The increase in VEGF-A levels in the experimental group was observed throughout the experiment compared to the control group. No significant changes in serum FGF-2 levels were found.
Conclusion:
The use of a foam massage roller increased VEGF-A serum levels, which may indicate stimulation of angiogenesis.
... Passive muscle stretch is a low-intensity stimulus for cardiocirculatory improvements that can be performed by healthy and clinical populations alike (11)(12)(13)(14)(15). When skeletal muscles are passively stretched and lengthened, capillary tortuosity and diameter are reduced, lowering capillary extension reserve and red blood cell flux and velocity (16)(17)(18)(19). ...
... Measurements of popliteal artery FMD were measured with an ultrasound system (Terason t3200, Burlington, MA) equipped with a multifrequency linear array transducer operating at 5 MHz and placed to avoid any bifurcation. This artery was selected as it is directly impacted by passive calf stretching and has been shown to be improved in patients with peripheral arterial disease (12,15,22). All measurements had a Doppler sample volume set at the full width of the vessel with the insonation angle <60 and were captured at rest and after cuff release (32). ...
... Reactive hyperemia created upon release of passive stretch could be linked to vessel deformation, increasing calcium release and subsequent NO production (39,40). These two factors appear to play a large role in the cardiocirculatory improvement (11,15,40). If passive stretch is performed repeatedly over the long term, improvements in microvascular reactivity, lowering of vascular stiffness, and increases to FMD have been reported (11,13). ...
Acute aerobic exercise stress is associated with decreased endothelial function that may increase the likelihood of an acute cardiovascular event. Passive stretch (PS) elicits improvements in vascular function, but whether PS can be performed before exercise to prevent declines in vascular function remains unknown. This strategy could be directly applicable in populations that may not be able to perform dynamic exercise. We hypothesized that preexercise PS would provide better vascular resilience after treadmill exercise. Sixteen healthy college-aged males and females participated in a single laboratory visit and underwent testing to assess micro- and- macrovascular function. Participants were randomized into either PS or sham-control. Intermittent calf PS was performed by having the foot in a splinting device for a 5-minute stretch, 5-minute relaxation, repeated 4 times. Then, a staged O2 peak test was performed and 65% O2 peak calculated for subjects to run at for 30-minutes. Near-infrared spectroscopy derived microvascular responsiveness was preserved with the PS group (pre: 0.53±0.009%/s), (post: 0.56±0.012%/s; p=0.55). However, there was a significant reduction in the sham control group (pre: 0.67±0.010%/s), (post: 0.51±0.007%/s; p=0.05) after treadmill exercise. Flow mediated vasodilation (FMD) of the popliteal artery showed similar responses. In the PS group, FMD (pre: 7.23±0.74%), (post: 5.86±1.01%; p=0.27) did not significantly decline after exercise. In the sham-control group FMD (pre: 8.69±0.72), (post: 5.24±1.24%; p<0.001) was significantly reduced after treadmill exercise. Vascular function may be more resilient if intermittent PS is performed prior to moderate intensity exercise and, importantly, can be performed by most individuals.
... Periods of immobilization or lower physical activity after serious injury [2,18,19] or pandemic lockdowns [20][21][22][23] as well as aging in general [24,25] result in significant loss of muscular performance including atrophy, decrease in maximal strength, loss of flexibility as well as musculoskeletal pain [26]. Morie et al. [27] and Hotta et al. [28] point out the need for safe and efficient alternatives to commonly used training and current therapies in rehabilitation settings to prevent loss of muscle performance and to restore maximal strength and flexibility. While different types of stretch training are known to improve flexibility [29][30][31][32][33], muscle Both training methods produce mechanical tension, which is a factor known to stimulate anabolic signaling and enhance protein synthesis. ...
... However, consideration of studies from Holly et al. [80] and Barnett [79] describing no increased electromyographic activity in the stretched muscles and Sola et al. [77] reporting reduced but still significant stretch-induced hypertrophy in denervated muscle, indicates that voluntary contractions against the stretching device may not be a pre-condition for hypertrophy. While Hotta et al. [28] pointed out a significantly reduced blood flow to the stretched muscle, further explanatory approaches, such as hypoxia, however, were not discussed in most animal studies. Notably, in humans, muscle blood flow restriction training has shown hypertrophic responses [131][132][133][134]. Additionally, because animals had to be dissected for examination, there was no real control group included in any of the listed studies, lowering the study quality. ...
... Apart from mechanical tension-induced signaling cascades, other explanations such as blood flow restriction [28,131,133] or neuromuscular adaptations [109,151] should be considered in further studies. Literature exploring the underlying physiological mechanisms in humans is scarce. ...
Increasing muscle strength and cross-sectional area is of crucial importance to improve or maintain physical function in musculoskeletal rehabilitation and sports performance. Decreases in muscular performance are experienced in phases of reduced physical activity or immobilization. These decrements highlight the need for alternative, easily accessible training regimes for a sedentary population to improve rehabilitation and injury prevention routines. Commonly, muscle hypertrophy and strength increases are associated with resistance training, typically performed in a training facility. Mechanical tension, which is usually induced with resistance machines and devices is known to be an important factor that stimulates the underlying signaling pathways to enhance protein synthesis. Findings from animal studies suggest an alternative means to induce mechanical tension to enhance protein synthesis, and therefore muscle hypertrophy by inducing high volume stretching. Thus, this narrative review discusses mechanical tension-induced physiological adaptations and their impact on muscle hypertrophy and strength gains. Furthermore, research addressing stretch-induced hypertrophy is critically analyzed. Derived from animal research, stretching literature exploring the impact of static stretching on morphological and functional adaptations was reviewed and critically discussed. No studies have investigated the underlying physiological mechanisms in humans yet, and thus the underlying mechanisms remain speculative and must be discussed in the light of animal research. However, studies that reported functional and morphological increases in humans commonly used stretching durations of >30 minutes per session of the plantar flexors, indicating the importance of high stretching volume, if the aim is to increase muscle mass and maximum strength. Therefore, the practical applicability seems limited to settings without access to resistance training (e.g., in an immobilized state at the start of rehabilitation), since resistance training seems to be more
time efficient. Nevertheless, further research is needed to generate evidence in different human populations (athletes, sedentary, and rehabilitation patients) and to quantify stretching intensity.
... Since blood flow restriction (BFR) training has the potential to increase MCSA [142,148,358] and many subjects described numbness in the foot of the stretched leg in the self-conducted studies, it cannot be ruled out that a reduced blood flow to the muscle is present while stretching and thus comparative adaptations might occur in long-lasting static stretching. Hotta et al. [141] also described decreased blood flow by using 30 minutes of stretching in the rat as an acute e↵ect but measured increased blood flow to the working muscle as a longterm e↵ect after a training period of four weeks on five days per week stretching training of 30 minutes which could possibly influence the strength performance in the target muscle. Though, it can be questioned whether and to which extent an increased blood flow to the working muscle can lead to improved maximal strength capacity. ...
... For the effects on fiber hypertrophy, an increase due to the stretching intervention was also determined (almost) 31. The changes in fiber cross-section ranged from − 0.75% to 141.6% (± 32.6%), with these two values being more of an outlier, as all other results ranged from + 27.8% to + 63.8% (see Table 5). ...
... While stretch training in humans is commonly used to improve flexibility, a meta-analysis of animal studies showed significant hypertrophic effects (Warneke et al. 2022b) with increases in muscle cross-sectional area of up to 141 (2010) showed the activation of this pathway due to muscle stretching. Based on very similar adaptations and underlying physiological responses, the question arises whether long-lasting stretch training could be used as an alternative to commonly used resistance training to induce significant increases in maximal strength and muscle thickness. ...
Stretching is primarily used to improve flexibility, decrease stiffness of the muscle- tendon unit or reduce risk of injury. However, previous animal studies from 1970 to 1990 showed significant hypertrophy effects in skeletal muscle in response to chronic stretching intervention with stretching durations of 30 minutes to 24 hours per day. However, no study in humans was performed using comparatively long stretching durations of more than 30 minutes per day with a daily frequency.
The present cumulative dissertation includes six studies aiming to investigate the effects of long-lasting static stretching training on maximum strength capacity, hypertrophy and flexibility in the skeletal muscle. Before starting own experimental studies, a meta-analysis of available animal research was conducted to analyze the potential of long-lasting stretching interventions on muscle mass and maximum strength. To induce long-lasting stretching on the plantar flexors and to improve standardization of the stretch training by quantifying the angle in the ankle joint while stretching, a calf muscle stretching orthosis was developed. In the following experimental studies, the orthosis was used to induce daily long- lasting static stretching stimuli with different stretching durations and intensities in the plantar flexors to assess different morphological and functional parameters. For this, a total of 311 participants were included in the studies and, dependent on the investigation, the effects of daily stretching for 10-120 minutes for six weeks were analyzed. Therefore, effects on maximal isometric and dynamic strength as well as flexibility of the plantar flexors were investigated with extended and flexed knee joint. The investigation of morphological parameters of the calf muscle was performed by determining the muscle thickness and the pennation angle by using sonographic imaging and the muscle cross-sectional area by using a 3 Tesla magnetic resonance imaging measurement.
In animals, the included systematic review with meta-analysis revealed increases in muscle mass with large effect size (d = 8.51, p < 0.001), muscle cross-sectional area (d = 7.91, p < 0.001), fiber cross-sectional area (d = 5.81, p < 0.001), fiber length (d = 7.86, p < 0.001) and fiber number (d = 4.62, p < 0.001). The thereafter performed experimental studies from our laboratory showed a range of trivial to large increases in maximum strength of 4.84% to 22.9% with d = 0.2 to 1.17 and ROM of 6.07% to 27.3% with d = 0.16 to 0.87 dependent on stretching time, training level and testing procedure. Furthermore, significant moderate to large magnitude hypertrophy effects of 7.29 to 15.3% with d = 0.53 to 0.84 in muscle thickness and trivial to small increases of 5.68% and 8.82% (d = 0.16 to 0.3) in muscle cross-sectional area were demonstrated.
The results are discussed based on physiological parameters from animal studies and in the front of knowledge in resistance training, suggesting mechanical tension to be one important factor to induce muscle hypertrophy and maximal strength increases. Further explanatory approaches such as hypoxia and changes in the muscle tendon unit are debated in the following. Since these studies are the first investigations on long-lasting stretch-mediated hypertrophy in humans, further research is needed to explore the underlying mechanisms and confirm the results in different populations to enhance the practical applicability for example in clinical populations when, e.g. counteracting muscular imbalances or sarcopenia in the elderly.
https://pub-data.leuphana.de/frontdoor/index/index/docId/1318
... Passive muscle stretch is a low-intensity stimulus for cardiocirculatory improvements that can be performed by healthy and clinical populations alike (11)(12)(13)(14)(15). When skeletal muscles are passively stretched and lengthened, capillary tortuosity and diameter are reduced, lowering capillary extension reserve and red blood cell flux and velocity (16)(17)(18)(19). ...
... Measurements of popliteal artery FMD were measured with an ultrasound system (Terason t3200, Burlington, MA) equipped with a multifrequency linear array transducer operating at 5 MHz and placed to avoid any bifurcation. This artery was selected as it is directly impacted by passive calf stretching and has been shown to be improved in patients with peripheral arterial disease (12,15,22). All measurements had a Doppler sample volume set at the full width of the vessel with the insonation angle <60 and were captured at rest and after cuff release (32). ...
... Reactive hyperemia created upon release of passive stretch could be linked to vessel deformation, increasing calcium release and subsequent NO production (39,40). These two factors appear to play a large role in the cardiocirculatory improvement (11,15,40). If passive stretch is performed repeatedly over the long term, improvements in microvascular reactivity, lowering of vascular stiffness, and increases to FMD have been reported (11,13). ...
Intermittent passive stretch induces local tissue hypoxia with subsequent increases in micro- and- macrovascular shear-rate, a powerful stimulus for nitric oxide generation in endothelial cells. Acute aerobic exercise stress has been associated with decreased endothelial function of the active limb. Whether intermittent passive stretch can reduce endothelial injury and improve endothelial function if performed before exercise has yet to be shown. This work investigated the impact of preexercise intermittent passive stretch on popliteal artery flow-mediated vasodilation (FMD) and the post occlusive reactive hyperemic (PORH) response within the gastrocnemius after aerobic exercise. We hypothesized that preexercise intermittent passive stretch of the calf muscles would prevent a decline in micro- and- macrovascular function after treadmill exercise. Sixteen healthy college-aged males and females participated in a single laboratory visit and underwent a PORH test with near-infrared spectrometry and FMD test to assess micro- and- macrovascular function. Participants were split into a PS group and a sham-control group performing minimal stretch. Intermittent passive calf stretching was performed by having participants place their foot in a splinting device for a 5-minute stretch, 5-minute relaxation period, repeated four times. Pre, post treatment, and post exercise time points were used in this investigation for analysis with a two-way repeated measures ANOVA and significance set at (P≤0.05). Following the treatment protocol, participants completed a VO 2 peak test to calculate 65% VO 2 peak and ran at this intensity for 30-minutes with post measurements taking place after a brief 10–20-minute recovery period. PORH with the NIRS revealed that microvascular responsiveness was preserved with the passive stretch group (pre: 0.053±0.009 %/s ⁻¹ ), (post: 0.051±0.013 %/s ⁻¹ ). There was a significant reduction (p=0.05) in the sham control group (pre: 0.072± 0.015 %/s ⁻¹ ), (post: 0.051±0.007 %/s ⁻¹ ) after treadmill exercise. Flow mediated vasodilation of the popliteal artery showed similar responses. In the passive stretch group, %FMD (pre: 7.58±0.88 %), (post: 6.40±1.21 %; p=0.27) and shear normalized FMD did not significantly decline after exercise (pre: 7.24 E-04 ±1.50 E-04 ), (post: 5.05 E-04 ±1.25 E-04 ; p=0.83). In the sham-control group %FMD (pre: 9.31±0.72 %), (post: 4.73±1.24 %; p<0.001) and normalized FMD were significantly reduced (pre: 1.06 E-03 ± 1.58 E-04 ), (post: 5.06 E-04 ±1.97 E-04 ; p<0.001). Passive stretch prior to acute exercise preserved popliteal artery endothelial function and gastrocnemius microvascular reperfusion. This vasoprotection was not shown in the sham-control group after acute exercise. Passive stretch is an easy low-cost method to maintain vascular function in the face of an acute exercise stress. Future work investigating adaptations to long term training when combined with preexercise stretch would be a valuable next step.
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This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
... Blood circulation in fascial tissue may play a critical role in maintaining the biomechanical, proprioceptive, and nociceptive function of the TLF [5,[22][23][24]. In particular, a decrease in blood flow with subsequent deoxygenation may be a trigger for fascial degeneration (e.g., stiffening, fibrosis, or thickening). ...
... In addition, hypoxia-related proteins are mediators of cell inflammation and apoptosis and cause a significant shift in collagen matrix and expression, which may also promote fascial degeneration [22]. On the other hand, fascial restrictions obviously decrease blood flow by vascular compression [24]. It is known from previous studies that fascial blood flow and oxygen saturation are dependent on individual physical activity (PA), age, and body mass index (BMI) [10,20,22,23,25,26]. ...
... Some studies have shown that hypoxia following circulation restriction can induce inflammation and apoptosis, leading to fascial degeneration [5,16,22,24]. Hoheisel et al. [16] and Mense [5] found a significantly increased density of substance p-positive fibers in inflamed rat TLF. These fibers are generally considered to be nociceptive [51] and could lead to higher pain sensitivity. ...
(1) Background: Inflammatory processes in the thoracolumbar fascia (TLF) lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood flow (BF) of fascial tissue may play a critical role in this process, as it may promote hypoxia-induced inflammation. The primary objective of the study was to examine the immediate effects of a set of myofascial release (MFR) techniques on the BF of lumbar myofascial tissue. The secondary objectives were to evaluate the influence of TLF morphology (TLFM), physical activity (PA), and body mass index (BMI) on these parameters and their correlations with each other. (2) Methods: This study was a single-blind, randomized, placebo-controlled trial. Thirty pain-free subjects (40.5 ± 14.1 years) were randomly assigned to two groups treated with MFR or a placebo intervention. Correlations between PA, BMI, and TLFM were calculated at baseline. The effects of MFR and TLFM on BF (measured with white light and laser Doppler spectroscopy) were determined. (3) Results: The MFR group had a significant increase in BF after treatment (31.6%) and at follow-up (48.7%) compared with the placebo group. BF was significantly different between disorganized and organized TLFM (p < 0.0001). There were strong correlations between PA (r = −0.648), PA (d = 0.681), BMI (r = −0.798), and TLFM. (4) Conclusions: Impaired blood flow could lead to hypoxia-induced inflammation, possibly resulting in pain and impaired proprioceptive function, thereby likely contributing to the development of nLBP. Fascial restrictions of blood vessels and free nerve endings, which are likely associated with TLFM, could be positively affected by the intervention in this study.
... They found that stretching practiced daily increases local blood flow through vasodilation, generating angiogenesis. 2 Other research teams led by Behnke conclude that the reduction in exercise capacity in older adults is due to decreased blood flow at the level of skeletal muscle, however vascularization in adults can improve with the help of physical activity. 3 Despite all the benefits shown during sports practice, this should be done in an appropriate environment and following a program in order to avoid injuries characteristic of each type of sports activity. ...
... Although this damage can be beneficial in the long term, it causes pain in the short term (between 24 and 72 hours) and is more evident in muscles that are not accustomed to the load. 2,20 Following muscle damage, the inflammatory response is activated in the body, which includes the release of various inflammatory mediators such as cytokines (Interleukins IL-1β, IL-6) and tumor necrosis factor alpha (TNFα), as well as prostaglandins. These mediators increase the permeability of blood vessels and attract immune cells to the affected area, sensitizing nerve endings and intensifying the perception of pain. ...
The pathogenesis of sports injuries is complex and difficult to identify clearly. Recent theories bring to light new mechanisms related to the production of muscle pain and tendinopathies. The accumulation of lactate can cause fatigue and muscle pain. Apparently, the lactate anion is an excellent fuel for myocardial fibre. Its accumulation of lactic acid after performing intense physical exercise can prevent the excitability of the sarcolemma induced by the increase in the concentration of the interstitial potassium ion. The identification of sports and physical activity that can cause damage to our body has become necessary, due to the increase in the incidence of joint injuries generated by physical activity in people who routinely practice exercise and in athletes, in order to prevent future injuries. Articles related to the different mechanisms involved in the different musculoskeletal injuries related to the practice of exercise have been selected.
... Stretching exercises lead to improvements in blood flow, decrease in arterial stiffness and increase in parasympathetic activation, resulting in decreases in BP. (Hotta et al., 2013;Hotta et al., 2018;Shinno et al., 2017). During stretching exercises, tension occurs not only in soft tissues, but also in vascular structures. ...
... The tension occurring in the vascular structures causes both structural changes and the release of vasodilator metabolites. These modifications reduce arterial stiffness, resistance to blood flow, and blood pressure (Hotta et al., 2018;Jackson et al., 2002;Kuebler et al., 2003). ...
Sitophilus species (Coleoptera: Curculionidae) are important pests on stored grains in the world. The Phosphine gas was applied to control the pests. But, the pests can develop resistance against phosphine. There are some studies about the role of endosymbiont bacteria in developing resistance to pesticides. This study was conducted to determine the presence of endosymbiont bacteria Wolbachia, Rickettsia, and Spiroplasma in phosphine-resistant and susceptible Turkish populations of two stored-product insects, granary weevil Sitophilus granarius and rice weevil S. oryzae. The infection rates in susceptible and resistant S. granarius populations were determined respectively for Wolbachia 49.7% and 87.2%, Rickettsia 45.6% and 37.5% and, Spiroplasma 27.8% ve 28.50%, and for S. oryzae 16.6% and 27.8 %, Rickettsia 33.3% and 77.8% and, Spiroplasma 11.2% and 5.6%. It can be said that endosymbionts have no effect on phosphine resistance.
... Stretching exercises lead to improvements in blood flow, decrease in arterial stiffness and increase in parasympathetic activation, resulting in decreases in BP. (Hotta et al., 2013;Hotta et al., 2018;Shinno et al., 2017). During stretching exercises, tension occurs not only in soft tissues, but also in vascular structures. ...
... The tension occurring in the vascular structures causes both structural changes and the release of vasodilator metabolites. These modifications reduce arterial stiffness, resistance to blood flow, and blood pressure (Hotta et al., 2018;Jackson et al., 2002;Kuebler et al., 2003). ...
Wheat is one of the most important crops cultivated in the world. The biggest post- harvest problem in wheat is the presence of storage pests. The granary weevil Sitophilus granarius (Coleoptera: Curculionidae), which causes serious product losses, is one of the important pests of wheat. Endosymbionts are commonly found in arthropods and have many different effects on them. So, they have the potential to be used in pest control. In this study, the presence of Wolbachia (W), Rickettsia (R), and Spiroplasma (S) endosymbionts and multiple infections were investigated in S. granarius individuals taken from five provinces representing four different regions of Turkey. Wolbachia, Rickettsia, and Spiroplasma infections were found to be 68.75%, 41.66%, and 37.50%, respectively. When it was looking at multiple infections, W+R, W+S, and W+R+S ratios were recorded as 16%, 18.75%, and 12%, however, S+R infection was not found
... Muscle stretching is a recommended CR pathway, which enhances the flexibility and movement of joints and prevents sports injuries and falls. Recent investigations reveal the vascular-beneficial effect of stretching in the peripheral arteries and capillarity in human and animal models (Hotta et al., 2019;Hotta et al., 2018). In a review and meta-analysis, Thomas et al. (2021) summarized some beneficial effects of muscle stretching on endothelial function and the cardiovascular system. ...
... In a review and meta-analysis, Thomas et al. (2021) summarized some beneficial effects of muscle stretching on endothelial function and the cardiovascular system. In patients with cardiovascular or endothelial dysfunction, stretching enhances endothelial function with upregulated NO release (Hotta et al., 2018;Thomas et al., 2021). Increased NO is confirmed in in vitro stretched vascular cells. ...
Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells (EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro- and microvasculature.
... Nevertheless, even though highly effective, there are a number of difficulties with common resistance training programs such as travelling to specialized training facilities to receive professional supervision. The lack of training success might not be attributable to the effectiveness of resistance training interventions per se, but to the participants limited motivation and commitment to travel to training locations or perform exhausting interventions [5,6]. The literature points out the high demand for time-and space-saving exercise alternatives which can be integrated into the participants or patients daily routines [7,8]. ...
... This study was performed to counteract methodological limitations described by Schoenfeld et al. [22] and others [5,6,14], indicating that long stretching durations were impractical. While increasing strength may potentially be particularly relevant for sportspecific tasks such as jumping and sprinting [46], or ball throwing velocity in handball [47], a recently published systematic review did not find stretch-induced performance enhancement [48], which seems in accordance with the lack of results for the rate of force development and explosive strength parameters obtained in the current study [15]. ...
Purpose: While there is reported superior effectiveness with supervised training, it usually re-quires specialized exercise facilities and instructors. Previous literature reported high volume stretching improved pectoralis muscles strength under supervised conditions while practical rel-evance is discussed. Therefore, the study objective was to compare the effects of volume equated, supervised- and self-administered home-based stretching on strength performance. Methods: Sixty-three recreational participants were equally assigned to either a supervised static stretch-ing, home-based stretching, or control group. The effects of 15 minutes pectoralis stretch; 4 days per week for 8 weeks were assessed on dynamic and isometric bench press strength and force de-velopment. Results: While there was a large magnitude maximal strength increase (p < 0.001 – 0.023, ƞ2= 0.118 – 0.351), force development remained unaffected. Dynamic maximal strength in both groups demonstrated large magnitude increases compared to the control group (p < 0.001 – 0.001, d=1.227 – 0.905). No differences between intervention group for maximal strength (p = 0.518 – 0.821, d = 0.101-0.322) could be detected. Conclusion: Results could potentially be at-tributed to stretch-induced tension (mechanical overload) with subsequent anabolic adaptations, while alternative explanatory approaches are discussed. Nevertheless, home-based stretching seems a practical alternative to supervised training with potential meaningful applications in different settings.
... Механічні розтягувальні подразники змінюють морфологію та функцію культивованих ЕК. У дослідженні K. Hotta та співавторів (2018 р.) визначено вплив щоденного розтягування м'язів на ендотелійзалежне розширення судин і доведено, що VEGF-A є вищим у м'язі розтягнутої кінцівки порівняно з нерозтягнутою контрлатеральною кінцівкою [14]. Циклічне розтягування спонукає судинні клітини гладких м'язів виділяти фактор росту сполучної тканини та сприяти диференціації клітин-попередників ЕК та ангіогенезу [30]. ...
... Циклічне розтягування спонукає судинні клітини гладких м'язів виділяти фактор росту сполучної тканини та сприяти диференціації клітин-попередників ЕК та ангіогенезу [30]. Експериментально доведено, що щоденне розтягування м'язів поліпшує кровотік, функцію ендотелію, капілярність, об'єм судин і зв'язок у скелетних м'язах [14]. ...
Angiogenesis is the process of formation of new blood vessels in tissues and organs, which occurs with the participation of many factors. Angiogenesis can be influenced by various factors, such as mechanical tissue stretching, hypoxia, infections, inflammation, and others. Understanding these mechanisms can be important for the development of new approaches to the treatment of various diseases associated with angiogenesis disorders. The process of angiogenesis plays an important role in various physiological and pathological conditions, such as wound healing, tissue regeneration, tumor development, and others. Regulation of angiogenesis can be used for the treatment of diseases associated with a lack of blood circulation. Knowledge about angiogenesis can also be useful for planning and conducting surgery, to increase the efficiency of the surgery, which can help significantly reduce the risk of complications, and avoid repeated interventions. Purpose - to search and analyze the recent publications to identify trends in the direction of influence on vascular growth. The search for publications was carried out in well-known global scientometric databases, the range of which spanned more than 10 years. Published results of many years of research, factors and methods of influence on angiogenesis were found and analyzed. To date, the questions of the impact on angiogenesis remain open, which calls for further research and study of new methods and improvement of existing ones, since knowledge about the mechanisms of angiogenesis can help to develop new methods of treatment and prevention of various diseases. No conflict of interests was declared by the authors.
... They found that daily muscle stretching increases local blood flow through vascular endothelium-dependent vasodilatation and determines angiogenesis. 2 Another study team led by Behnke concluded that the decrease in exercise capacity in the elderly is due to the decrease in blood flow in the striated skeletal muscles. Therefore, muscle vascularization in old age can be improved with the help of physical exercise supported by increasing blood flow. ...
... Therefore, muscle vascularization in old age can be improved with the help of physical exercise supported by increasing blood flow. 2,3 Despite all these benefits, the practice of sports must be carried out in a controlled environment and according to a predetermined program to prevent the injuries characteristic of each type of sports activity. For the optimal management of musculotendinous and fascial injuries, as well as for the recovery of athletes' capacity, a better understanding of the pathogenic mechanism of traumatic injuries is necessary. ...
Purpose
The identification of sports and physical exercises with injury risk is necessary to preserve the capacity of athletes and people who perform physical education and also to prevent the installation of functional deficiencies.
Methods
We have selected the articles related to the pathogenic mechanisms involved in musculotendinous and fascial injuries produced as a result of physical exercise.
Results and Discussions
The lesional pathogenesis is complex and incompletely clarified. Recent theories put in a new light the mechanisms of muscle pain and tendinopathy production. The accumulation of lactate anion, known to be a residue that induces fatigue and muscle pain, has been reconsidered by some authors. It appears that lactate anion is an excellent fuel for the myocardial fiber. Moreover, the accumulation of lactic acid after intense physical exercise could prevent the inexcitability of the sarcolemma induced by the increased concentration of interstitial K⁺. Most of the time, overuse injuries are not limited to muscles. They can cause myofascial, myotendinous or purely muscular injuries. The muscular fascia is more susceptible to injuries produced under the action of large external forces. Also, fascia is more sensitive to pain compared to muscle when external forces act eccentrically. Overloading the tendon and putting it under tension repeatedly is followed by ruptures of the tendon fibers. The regeneration of the degenerated tendon is defective in the context of the inflammation produced by the injury. Tendon fibers undergo a process of fibrosis, scarring, adhesion and heterogeneous calcification. Oxidative stress is responsible for inflammation, degeneration and apoptosis of tenocytes.
Conclusion
The benefits brought by physical education and sports are indisputable, but their practice requires a coordinated program to prevent possible traumatic and overuse injuries.
... Research shows that stretching the muscles enhances vasodilation and stimulates angiogenesis, which increases blood flow through the muscles [33]. Additionally, it has been shown that lower limb stretching exercises improve the balance in the geriatric population This is due to favourable changes in proprioception and modifications within muscles, tendons and fascia [33]. ...
... Research shows that stretching the muscles enhances vasodilation and stimulates angiogenesis, which increases blood flow through the muscles [33]. Additionally, it has been shown that lower limb stretching exercises improve the balance in the geriatric population This is due to favourable changes in proprioception and modifications within muscles, tendons and fascia [33]. Improving flexibility increases mobility ranges (and reduces the feeling of stiffness), which translates into improved walking, lengthening of the stride and capability to react when trying to maintain balance [34,35]. ...
Frailty syndrome, otherwise known as weakness or decline in physiologic reserve syndrome, is an important health problem for an aging population. According to the definition, it is a syndrome characterized by a decrease in the body’s physiologic reserves as a result of the accumulation of reduced efficiency of many organs and systems. The prevalence of frailty increases with age, it is intensified by the burden of chronic diseases and limitation of physical fitness. Symptoms of frailty may appear before the age of 65, although the incidence worsens in people who are 70 and older. The consequence of frailty is limited resistance to stressors and the associated susceptibility to disproportionate deterioration of the patient’s health. It has been shown that the frailty syndrome is a dynamic and partially reversible condition, therefore, it is important to introduce preventive measures which will reduce the development of frailty and contribute to improvement of health. One of the most important interventions in the prevention and treatment of frailty syndrome is regular and properly planned physical activity. The aim of the publication is to summarize the current knowledge and guidelines on planning an optimal physical activity program for this group of patients.
... The faster the stretch, the higher the muscle stiffness will be [6]. Most stretching techniques (static, dynamic, ballistic, etc.) have been successfully implemented in clinical practice [2,4,24,25]. ...
... The additional effects of individual training status, age, sex, and different pathological states that moderate the influences of stretching exercises on the joints, muscles, tendons, and ligaments can be characterized as indirect [6,18,22,24,35]. ...
Characterized in biomedical terms, stretching exercises have been defined as movements applied by external and/or internal forces to increase muscle and joint flexibility, decrease muscle stiffness, elevate the joint range of motion (ROM), increase the length of the “muscle–tendon” morpho-functional unit, and improve joint, muscle, and tendon movements, contraction, and relaxation. The present review examines and summarizes the initial and recent literature data related to the biomechanical, physiological, and therapeutic effects of static stretching (SS) on flexibility and other physiological characteristics of the main structure and the “joint–ligament–tendon–muscle” functional unit. The healing and therapeutic effects of SS, combined with other rehabilitation techniques (massage, foam rolling with and without vibrations, hot/cold therapy, etc.), are discussed in relation to the creation of individual (patient-specific) or group programs for the treatment and prevention of joint injuries, as well as for the improvement of performance in sports. From a theoretical point of view, the role of SS in positively affecting the composition of the connective tissue matrix is pointed out: types I–III collagen syntheses, hyaluronic acid, and glycosaminoglycan (GAG) turnover under the influence of the transforming growth factor beta-1 (TGF-β-1). Different variables, such as collagen type, biochemistry, elongation, and elasticity, are used as molecular biomarkers. Recent studies have indicated that static progressive stretching therapy can prevent/reduce the development of arthrogenic contractures, joint capsule fibrosis, and muscle stiffness and requires new clinical applications. Combined stretching techniques have been proposed and applied in medicine and sports, depending on their long- and short-term effects on variables, such as the ROM, EMG activity, and muscle stiffness. The results obtained are of theoretical and practical interest for the development of new experimental, mathematical, and computational models and the creation of efficient therapeutic programs. The healing effects of SS on the main structural and functional unit—“joint–ligament–tendon–muscle”—need further investigation, which can clarify and evaluate the benefits of SS in prophylaxis and the treatment of joint injuries in healthy and ill individuals and in older adults, compared to young, active, and well-trained persons, as well as compared to professional athletes.
... These adaptations result in increased production of vascular endothelial growth factor that increase the lifespan of endothelial cells, prevents apoptosis and promotes capillarization that lead to decreased vascular resistance, which could potentially decrease blood pressure. 10 Another mechanism by which stretching can affect blood pressure is stretching of blood Volume 8; Issue: 2; April-June 2023 vessels induces the release of metabolites from endothelial cells that cause vasodilatation. A study reported that stretching exercises of knee extensors and plantar flexors for twelve weeks by performing four stretches five times each for forty-five seconds, five sessions per week are evident in increasing flow mediated dilation which is dependent on nitric oxide release. ...
... A study reported that stretching exercises of knee extensors and plantar flexors for twelve weeks by performing four stretches five times each for forty-five seconds, five sessions per week are evident in increasing flow mediated dilation which is dependent on nitric oxide release. 10 A final mechanism by which stretching can affect blood pressure is by its effect on sympathetic and parasympathetic nervous systems. Performing an acute bout of stretching exercise can reduce activation of sympathetic nervous system along with an increased activation of the parasympathetic nervous system. ...
Hypertension is the major risk factor for different cardiovascular diseases like ischemic heart disease, congestive heart failure, stroke and chronic kidney disease. Best estimates suggest that 57% of stroke and 24% of coronary artery disease-related deaths are due to hypertension. Various physical exercises such as aerobic exercises, resistance exercises, high intensity interval training performed regularly can help with management of blood pressure, quality of life and cardiovascular complications. Static stretching of the skeletal muscles accrues the benefits of exercise without its accompanying physical stress as in case of aerobic exercise and resisted exercises. Studies have supported that stretching could results in better control of blood pressure in normotensive patients. Also, few studies have been done on hypertensive patients, but have multiple limitations. Studies conducted till date could not conclude definitive conclusion for framing a definitive protocol of stretching exercises in patients with hypertension. Hence, in order to establish a definitive stretching protocol in patients with hypertension further researches needs to be conducted.
... ET-1 interferes with the insulin signaling leading to an insulin resistance [9] where the ETAR along with ET-1 will inhibit insulininduced Akt phosphorylation plus [3H]2-DG uptake depending in a Gq/11 protein-and GRK2 manner in skeletal muscle tissue; thus, ridding the vessel not only of the vasodilatation effect but to its anabolic effect which in the end helps to maintain protein synthesis and the anabolic state above the catabolic one. ...
... So how can we target and ease this tormented and hateful relationship between the ET-1 signaling and the skeletal muscle tissue. Well indeed we can from the pharmacologic point of view till the healthy lifestyle including physical activity point of view [6,[9][10][11]. ...
... The physiological rationale behind incorporating inter-set stretching into RT revolves around several key mechanisms, such as increased time under tension (and therefore, training volume) and neuromuscular, metabolic, and hormonal responses [10], factors that are associated with strength gains and hypertrophy [10]. Stretching can increase blood flow to the muscles [11,12], facilitating the removal of metabolic by products like lactate, which can contribute to muscle recovery and fatigue prevention. Furthermore, inter-set stretching might influence the muscle's length-tension relationship, potentially increasing the muscle's ability to generate force [13,14]. ...
Purpose
This study aimed to evaluate the effect of static stretching performed between sets of resistance training with flywheels on muscle adaptations.
Methods
Twenty men (19.65 ± 1.35 years) were allocated to two experimental conditions: (a) resistance training protocol (RT) or (b) TR protocol + 120 s of static stretching between sets (SSRT). The resistance training was conducted 3 days a week for 8 weeks, with progressively increased training volume throughout the sessions.
Results
There were no significant differences between the two experimental conditions for anthropometric variables (p > 0.05), for the different manifestations of strength evaluated (p > 0.05) and for the muscle activation of the different muscles evaluated in MVIC and 1 RM test (p > 0.05). However, it alters the muscle activation at power exercises at 80% of 1 RM (p < 0.05). SSRT achieved an increase in hip flexibility (p = 0.04), while the group without stretching showed no significant differences.
Conclusion
Stretching between sets from RT does not decrease strength, does not alter muscle activation evaluated in MVIC and 1 RM test, volume, and internal training load, when compared to the same protocol, without performing previous stretching.
... In this case, such intensity is not favorable for post-COVID-19, considering that the virus has a high inflammatory potential. The same study states that anti-inflammatory activation occurs at low intensity, with low-intensity stretching being the most suitable for post-COVID-19, considering its low pro-inflammatory response and its anti-inflammatory activation 19 . A review study 12 from 2020 concludes that stretching has positive effects on balance, both acutely and chronically, improving the quality of life for individuals with low balance, with a particular focus on the elderly. ...
Background: COVID-19 is a new disease that causes severe health problems and is responsible for significant complications even after recovery, including disabilities that lead to motor impairment. In this sense, there is currently no protocol for physical exercises for people with physical disabilities caused by the disease. Therefore, it is necessary to find ways for individuals affected by this condition and experiencing motor difficulties to engage in physical activities, preventing their condition from deteriorating further after COVID-19. Objective: To present evidence that stretching improves strength, respiratory and vascular system function, enabling the return of individuals with physical deficits who are hindered from performing activities of daily living. Methods: This study is a literature review that analyzes the correlation between the benefits of active static stretching in individuals with physical disabilities post-COVID-19. The study collected data through accumulated scientific knowledge in the fields of clinical health and physical activity. The literature search was conducted using digital scientific databases, including SciELO, ScienceDirect, Bireme, and Google Scholar. Results: Muscle stretching is a physical activity that has shown promising benefits for post-COVID patients, however, further research in this field is needed. Conclusion: Through the presented studies, it can be concluded that stretching is a type of exercise that potentially can counterbalance various sequels caused by COVID-19, enabling the affected person to return to their daily routines.
... SS and aerobic exercise are thought to promote nitric oxide (NO) production by increasing shear stress on vascular endothelial cells and increased blood flow, respectively [21,22]. Continuous exercise and SS also have angiogenic effects [23,24]. CAVI is reduced by collateral blood vessels formed owing to neovascularization [25]. ...
Proliferative diabetic retinopathy (PDR) and peripheral arterial disease (PAD) of the lower extremities are serious complications of type 2 diabetes mellitus (T2DM). Aerobic exercise has been shown to be primarily effective for glycemic control and gait disturbance owing to PAD. However, the safety and efficacy of exercise therapy in patients with PDR remain unclear. The purpose of this case report was to demonstrate the short-term effects of static stretching (SS) and daily walking over 10,000 steps on patients with T2DM presenting with PDR and PAD. The intervention consisted of 40 minutes of other-movement SS and in-hospital walking during a two-week hospitalization phase and 20-30 minutes of automatic SS and outdoor walking during a two-week home phase post-discharge. The walking conditions consisted of 10,000 steps/day, and the rate of perceived exertion was 11-12 on the Borg scale. Outcomes included the presence of a new intraocular hemorrhage and changes in intraocular pressure (IOP), blood pressure, fasting blood glucose level, biochemical parameters, cardio-ankle vascular index (CAVI), and ankle-brachial index. No new intraocular hemorrhage or increased IOP was observed during the intervention period, and blood pressure, glycemic control, and CAVI parameters improved. The results of the intervention in this case suggest that the combination of SS and walking exercises may be safe and effective.
... Regular physical activity exerts beneficial effects on cardiovascular health through multiple physiological mechanisms, including improvements in lipid and triglycerides metabolism, blood pressure regulation, insulin sensitivity, and endothelial function. Additionally, physical activity enhances endothelial function by promoting nitric oxide production, leading to vasodilation and improved blood flow, thereby reducing hypertension, and enhancing vascular health [31][32][33]. Moreover, a plethora of research underscores the pivotal role of physical activity in glucose metabolism and insulin sensitivity, shedding light on its potential mechanisms [34]. ...
Objective
To evaluate trends in physical activity levels and their associations with demographic characteristics, health status, and lifetime cardiovascular disease (CVD) risk.
Methods
A longitudinal analysis was conducted using data from 987 males and 1,001 females (45 ± 12 years old) participating in the ATTICA cohort study. Physical activity levels were assessed at baseline (2001-2002) and subsequent follow-ups (2006, 2012, and 2022). Four physical activity trajectories according to participants’ physical activity tracking were defined, i.e., consistently active/inactive and changed from active/inactive. Twenty-year incidence of hypertension, hypercholesterolemia, and diabetes were evaluated in relation to physical activity trajectories; the life-table method was utilized to forecast the lifetime CVD risk (death without CVD was regarded as a competing event).
Results
in total, 47% of the participants were categorized as being consistently inactive, whereas only 9% of males and 15% of females sustained physical activity levels throughout the 20-year follow-up period (p < 0.001). Participants being consistently inactive were from lower socioeconomic backgrounds (p = 0.002). Transitioning to being physically active was associated with higher education level and being married (p < 0.001). Consistently active individuals had up to 35% reduced lifetime CVD risk, and lower 20-year incidence of hypertension, and hypercholesterolemia (p < 0.01); no association was observed regarding diabetes incidence.
Conclusions
Promoting and maintaining regular physical activity throughout lifespan is crucial for reducing lifetime CVD risk and related risk factors. Tailored interventions addressing demographic and socioeconomic factors may help enhance cardiovascular health outcomes.
... The inclusion of stretching exercises in almost one-third of the daily session was due to several reasons: (1) the positive effect of stretching on adaptations of endothelial function and muscle blood flow in elderly rats, increasing microvascular volume, the number of capillaries per muscle fiber, levels of hypoxia-induced factor-1α, vascular endothelial growth factor, and endothelial nitric oxide synthase [62], (2) increased shoulder range of motion and a decrease in chest tightness and pain after breast cancer surgery [63,64], (3) reduction in tumor growth due to restoration of cytotoxic immunity by reversing the impairment of cytotoxic CD8+ T lymphocytes and activation of T cells, which play a central role in immune defense [65], (4) furthermore, resolvin D1 (RvD1) and resolvin D2 (RvD2), pro-resolving lipid mediators (SPM) with anti-inflammatory properties [66,67], were significantly higher in stretched mice compared to control mice [65,66], reducing acute inflammation. Therefore, improvements in quality of life and reduction in fatigue could be attributed to the performance of exercises. ...
Background: Due to their high toxicity, cancer treatments produce multiple sequelae, including fatigue, which has a great impact on quality of life. Therefore, the aim of this study is to evaluate the efficacy on quality of life, fatigue, and functional capacity of a short-term exercise program combining aerobic exercise, resistance training, and stretching for 6 weeks in cancer patients. Methods: The design of the study was quasi-experimental, which included a group of 30 women who were receiving or had received in the last year chemotherapy, radiotherapy, or hormonal treatment. The exercise supervised program with vigorous intensity lasted for six weeks and consisted of three distinct blocks: aerobic exercise (25 min), resistance training (20 min), and stretching exercises (15 min). Before and after starting the exercise program quality of life (EORTC QLQ-C30 questionnaire), functional capacity [6 min Walking Test (6MWT), Handgrip Test (HGT), 30-Second Sit-to-Stand Test (30s-STST)], and fatigue (FACIT-F questionnaire) were measured. Results: In the EORTC QLQ-C30 questionnaire significantly higher scores were observed in the global health status scale (p < 0.05), as well as in the functional scale in the role functioning, emotional functioning, and cognitive functioning items (p < 0.05), indicating a higher quality of life and overall health level. There was also a reduction in fatigue (p < 0.05), obtaining higher scores on the FACIT-F questionnaire after the exercise program. Additionally significant improvements are observed in 6MWT, HGT, and 30s-STST following the implementation of the exercise program (p < 0.05). Conclusions: A 6-week exercise protocol, with a vigorous intensity, including resistance training, endurance, and stretching exercises can produce significant improvements in quality of life and reduction in fatigue, as well as improve muscle strength and functional capacity.
... This suggests that vascular endothelial function may play a critically important role in the triad between exercise, hypertension, and migraine. Specifically, during exercise, increased blood flow shear stress stimulates endothelial cells and promotes the upregulation of endothelial nitric oxide synthase (eNOS) and VEGF expression [71]. These changes contribute to the enhancement of endotheliumdependent vasodilatation while inducing neovascularization, thereby improving systemic vascular endothelial function [68]. ...
Background
The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality.
Methods
Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set. Estimates derived from the two datasets were combined using fixed-effects meta-analysis. Two-step univariable MR (UVMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to evaluate 19 potential mediators of association and determine the proportions of these mediators.
Results
The combined effect of inverse variance weighted revealed that a one standard deviation (SD) increase in genetically predicted Leisure screen time (LST) was associated with a 27.7% increase (95% CI: 1.14–1.44) in migraine risk, while Moderate or/and vigorous physical activity (MVPA) was associated with a 26.9% decrease (95% CI: 0.61–0.87) in migraine risk. The results of the mediation analysis indicated that out of the 19 modifiable metabolic risk factors examined, hypertension explains 24.81% of the relationship between LST and the risk of experiencing migraine. Furthermore, hypertension and diastolic blood pressure (DBP) partially weaken the association between MVPA and migraines, mediating 4.86% and 4.66% respectively.
Conclusion
Our research findings indicated that both LST and MVPA in lifestyle have independent causal effects on migraine. Additionally, we have identified that hypertension and DBP play a mediating role in the causal pathway between these two factors and migraine.
... Substantial microcirculatory events have been observed up to 10 min after stretching itself, such as post-stretch hyperaemia (16). Subsequent evidence has shown that these microcirculatory events can also be observed in the long term: after 4 weeks of muscle stretching, an increase in blood flow in the stretched limb was observed during exercise on the treadmill, compared to the contralateral non-stretched limb (17). This evidence demonstrates that stretching exercises administered after a training session can influence the recovery capacity, even regarding peripheral muscle microcirculation (18,19) because of the production and release of nitric oxide (20). ...
Previous research has demonstrated that stretching can enhance athletic performance and induce cardiovascular adaptations. This study aims to assess whether a 4-week preventative stretching routine can enhance heart rate variability and heart rate recovery, faster blood lactate clearance, and improve performance following submaximal strength exercises. Twenty-four healthy adults were recruited and randomly allocated to either the experimental group or the control group. Both groups engaged in submaximal strength exercises (5 sets to voluntary failure at 60% of 1RM) comprising bench press and back squat exercises under baseline conditions and after stretching protocol. The experimental group followed the Stretching Protocol, while the control group adhered to their regular training routine. ANOVA analysis revealed a significant pre-post interaction effect between groups in the variable of squat repetitions, although no notable pre- or post-differences were observed in heart rate variability, heart rate recovery, blood lactate concentration, or bench repetitions in either group. A 4-week preventative stretching program does not appear adequate to enhance lactate clearance and cardiovascular adaptation after submaximal strength exercises in resistance-trained individuals compared to the control group. However, it is plausible that such a stretching routine may mitigate muscle fatigue, though further investigation is warranted to substantiate this hypothesis.
... However, even though significant, Wohlann et al. [32] critically discussed the magnitude of such CK increases as clinically irrelevant. Another possibility from a rat study suggests that prolonged static stretching can restrict muscle blood flow [33], which could adversely impact metabolic activity [34] and cause fatigue [35] and thus impair force [36]. However, as there are no studies investigating structural stretching effects, this explanation remains speculative. ...
Purpose: The stretch-induced force deficit suggests an acute stretch-specific strength capacity loss, which is commonly attributed to EMG reductions. Since those could also be attributed to general fatigue induced by overloading the muscle, this study aimed to compare stretching with an ex-hausting calf raise programme to compare strength and flexibility responses.
Method: This study included 16 participants different, high duration calf muscle stretching ef-fects (10, 20, 30 minutes of stretching) with a resistance training (RT) (3x12 repetitions) performed until muscle failure, by using a cross-over study design with pre-post comparisons. Strength was tested via isometric plantar flexor diagnostics, while flexibility was assessed using the knee-to-wall test (KtW) and an isolated goniometer test.
Results: Using a three-way ANOVA, RT strength decreases were greater compared to 10 & 20min of stretching (p=0.01 – 0.02), but similar to those of 30 minutes of stretching. ROM in the KtW showed no specific stretch-induced increases, while only the stretching conditions enhanced isolated tested ROM (p<0.001–0.008). No RT related isolated ROM increases were observed.
Conclusion: The results showed both interventions had similar effects on strength and ROM in the calf muscles. More holistic explanatory approaches such as fatigue and warm-up are dis-cussed in the manuscript and call for further research.
... Considerable structural adaptations were reported in response to blood flow restriction [190], which were potentially initiated by similar physiological pathways [191] including the mTOR signalling pathway [192], with Gundermann et al. [193] showing stimulation of mTORC1 and muscle protein synthesis immediately after blood flow restriction training. Interestingly, in the rat muscle, Hotta et al. [194] described an almost complete suppression of the blood flow to the stretched muscle. Thus, potential stimulating effects of restricted blood flow on structural adaptations cannot be ruled out, while stretch-induced changes in blood flow patterns in human muscle have not been comprehensively investigated, while no studies were found that showed an increased flexibility in response to blood flow restriction training. ...
The mechanisms underlying range of motion enhancements via flexibility training discussed in the literature show high heterogeneity in research methodology and study findings. In addition, scientific conclusions are mostly based on functional observations while studies considering the underlying physiology are less common. However, understanding the underlying mechanisms that contribute to an improved range of motion through stretching is crucial for conducting comparable studies with sound designs, optimising training routines and accurately interpreting resulting outcomes. While there seems to be no evidence to attribute acute range of motion increases as well as changes in muscle and tendon stiffness and pain perception specifically to stretching or foam rolling, the role of general warm-up effects is discussed in this paper. Additionally, the role of mechanical tension applied to greater muscle lengths for range of motion improvement will be discussed. Thus, it is suggested that physical training stressors can be seen as external stimuli that control gene expression via the targeted stimulation of transcription factors, leading to structural adaptations due to enhanced protein synthesis. Hence, the possible role of serial sarcomerogenesis in altering pain perception, reducing muscle stiffness and passive torque, or changes in the optimal joint angle for force development is considered as well as alternative interventions with a potential impact on anabolic pathways. As there are limited possibilities to directly measure serial sarcomere number, longitudinal muscle hypertrophy remains without direct evidence. The available literature does not demonstrate the necessity of only using specific flexibility training routines such as stretching to enhance acute or chronic range of motion.
... Especially since the only significant correlation was obtained between fascia stiffness and ROM improvements, future studies are required to confirm our findings. Second, although we did not find differences between muscle and fascia immediately post-intervention, this could well be the case at later time points as production of relevant fluids such as hyaluronic acid in the fascia and blood flow in the muscle and fascia might occur after removing the stretching stimulus (Hotta et al. 2018). Future studies may thus consider including additional follow-up measurements. ...
Aim
Previous stretching studies mostly investigated effects on the skeletal muscle but comprehensive explorations regarding the role of the connective tissue are scarce. Since the deep fascia has been demonstrated to be sensitive to mechanical tension, it was hypothesized that the fascia would also respond to stretching, contributing to enhanced range of motion (ROM).
Methods
Forty (40) recreationally active participants (male: n = 25, female: n = 15) were included in the randomized controlled cross-over trial and allocated to different groups performing 5 min static (STAT) or dynamic (DYN) plantar flexor stretching or control condition (CC) in a random order. Pre- and immediately post-intervention, muscle and fascia stiffness, as well as muscle and fascia thickness were measured using high-resolution ultrasound and strain elastography. ROM was assessed in the ankle joint via the knee to wall test (KtW) and goniometer.
Results
STAT reduced both, muscle and fascia stiffness (d = 0.78 and 0.42, p < 0.001, respectively), while DYN did not reduce stiffness compared to the control condition (p = 0.11–0.41). While both conditions showed significant increases in the KtW (d = 0.43–0.46, p = 0.02–0.04), no significant differences to the CC were observed for the isolated ROM testing (p = 0.09 and 0.77). There was a small correlation between fascia stiffness decreases and ROM increases (r = − 0.25, p = 0.006) but no association was found between muscle stiffness decreases and ROM increases (p = 0.13–0.40).
Conclusion
Our study is the first to reveal stretch-induced changes in fascia stiffness. Changes of fascia`s but not muscle`s mechanical properties may contribute to increased ROM following stretching.
... Interestingly, Jessee et al. [93] showed that blood flow restriction induces hypertrophy, however, it seems of minor relevance for maximum strength increases. Hotta et al. [94] observed acute decreases of blood flow during 30 min of stretching in animals. Studies measuring the metabolic muscle response to stretching would thus be warranted in order to further delineate the potential relevance of the abovementioned factors. ...
Background
Increases in maximal strength and muscle volume represent central aims of training interventions. Recent research suggested that the chronic application of stretch may be effective in inducing hypertrophy. The present systematic review therefore aimed to syntheisize the evidence on changes of strength and muscle volume following chronic static stretching.
Methods
Three data bases were sceened to conduct a systematic review with meta-analysis. Studies using randomized, controlled trials with longitudinal (≥ 2 weeks) design, investigating strength and muscle volume following static stretching in humans, were included. Study quality was rated by two examiners using the PEDro scale.
Results
A total of 42 studies with 1318 cumulative participants were identified. Meta-analyses using robust variance estimation showed small stretch-mediated maximal strength increases (d = 0.30 p < 0.001) with stretching duration and intervention time as significant moderators. Including all studies, stretching induced small magnitude, but significant hypertrophy effects (d = 0.20). Longer stretching durations and intervention periods as well as higher training frequencies revealed small (d = 0.26–0.28), but significant effects (p < 0.001–0.005), while lower dosage did not reach the level of significance (p = 0.13–0.39).
Conclusions
While of minor effectiveness, chronic static stretching represents a possible alternative to resistance training when aiming to improve strength and increase muscle size. As a dose-response relationship may exist, higher stretch durations and frequencies as well as long program durations should be further elaborated.
... On the other hand, studies have shown muscle stretching improved postural parameters, including CVA flexion ROM in females with FHP [65]. The proposed mechanical effects of stretching exercise on the shortened muscles include improved flexibility, blood circulation, and stretching of contracted cytoskeletal structures, reducing the overlap of actin and myosin filaments [66][67][68]. Hence, in the present study, maybe part of the effects is related to stretching exercise. ...
Introduction: Forward head posture (FHP) is one of the most common positional deviations. Frequent users often exhibit incorrect posture because of the rising popularity of media devices, such as smartphones and computers. This posture leads to changes in muscle activity in cervical flexion and extension. It is defined by hyperextension of the upper cervical vertebrae and forward translation of the cervical vertebrae. This study evaluates the effect of dry needles as a new method in the upper trapezius muscle on the neck’s angles and range of motion (ROM) in individuals with FHP Materials and Methods: In this quasi-experimental interventional study, 18 women with FHP underwent a dry needle session. The photogrammetry of the cranio-vertebral angle measured the degree of FHP. Visual analog scale (VAS), pain pressure threshold (PPT), cranio-vertebral angle (CVA) and cranio-horizontal angles (CHA), ROM, scapular index (SI), and forward shoulder translation (FST) were assessed before and after the intervention. Results: The results demonstrated that after the intervention, right and left PPT, flexion, and proper neck rotation, right and left SI, CVA, and CHA were significantly improved (P<0.05). Conclusion: The results showed that one session of dry needling with stretching exercises intervention could improve PPT, ROM, SI, CVA, and CHA and consequently improve FHP.
... Besides, four [3,24,54,56] of the included participants in these six studies [3,24,46,51,54,56] were young, with an average age between 20 and 30 years, while the other two [46,51] included both young and middle-aged people, but all were under 60 years of age. Previous studies have shown that middle-aged and elderly people are more likely to present loss of ROM and soft tissue extension due to decreased muscle mass and exercise due to increased age and the deterioration of physical function [61]. The study by Zhou Wen-Sheng et al. [45] also explained why stretching effectively improved ROM in older people. ...
Introduction:
Hamstring injuries are one of the most common types of damage in sports. Insufficient flexibility and high stiffness are important reasons for it. Stretching is often used in warm-up activities before exercises to increase flexibility, among which dynamic stretching (DS) and static stretching (SS) are the most widely used. The effects of these two stretching techniques on the flexibility or stiffness of the hamstring still need to be clarified.
Objective:
This study aimed to compare the short-term, medium-term, and long-term effects of DS and SS on improving hamstring flexibility and stiffness via a meta-analysis of RCTs.
Methods:
RCTs were identified from PubMed, Cochrane Library, Web of Science, and PEDro from inception to July 28, 2022. The methodological quality was evaluated using the PEDro scale. The mean difference and 95% confidence interval of the outcome variables before and after stretching were calculated and the extracted data were quantitatively processed using a random or fixed effects model.
Results:
A total of 27 RCTs and 606 participants were included. In terms of improving the ROM of the hamstring, there was no significant difference in the acute (MD, -0.70, 95% CI, -1.54 to 0.14; Z = 1.63, P > 0.05) and sub-acute effects (MD, 1.71, 95% CI, -2.80 to 6.22; Z = 0.74, P > 0.05) between a single bout of SS and DS, while the acute (MD, -5.13, 95% CI, -7.65 to -2.61; Z = 3.99, P < 0.05) and sub-acute effects (MD, -5.30, 95% CI, -6.33 to -4.27; Z = 10.04, P < 0.05) of multiple bouts of SS was superior to DS; There was no significant difference in the medium-term effect between the two stretching techniques (MD, 3.48, 95% CI, -2.57 to 9.53; Z = 1.13, P > 0.05), but the long-term effect of SS was better than DS (MD, - 10.40, 95% CI, -10.97 to -9.83; Z = 35.57, P < 0.05). Regarding the length of the hamstring, the acute (MD, -0.41, 95% CI, -1.09 to 0.26; Z = 1.20, P > 0.05) and sub-acute effects (MD, -0.73, 95% CI, -1.69 to 0.22; Z = 1.51, P > 0.05) of a single bout of DS and SS were similar. Two studies have compared the effects on hamstring stiffness, with one showing similar effects, and the other showed that DS was superior to SS. One study showed no difference in the magnitude of change in improving passive torque. No studies explored the effect of DS and SS on hamstring myofascial length. Only one study demonstrated no significant difference in hamstring thickness.
Conclusions:
A single bout of DS and SS have similar short-term effects in improving hamstring ROM and length, while multiple bouts of SS can significantly improve hamstring ROM compared to DS. DS and SS showed similar effects on hamstring myofascial length.
... Occlusion training, defined as blood flow restriction training, has also shown an increase in diastolic and systolic blood pressure, heart rate, stroke volume, and cardiac output in older women (173). Endothelium-dependent vasodilation of skeletal muscle, angiogenic markers, and capillarity also show a positive response to flexibility training (174), which is a good alternative in older populations. High intensity exercise can lead to greater improvements in aerobic capacity and cardioprotective effect (175), in addition to endothelial function and quality of life (176), from which it is inferred that the exercise intensity can have an impact on its protective effect at the cardiovascular level and can be an important factor in maintaining and/or improving the aerobic capacity of older adults. ...
Aging is an inherent process to living beings that involves a deterioration of homeostatic regulation and functional reserve. Currently, the aging population has high levels of physical inactivity that aggravates muscle disuse, which in turn drastically affects functional capacity and quality of life. The aim of this narrative review is to present aging conditions and the protective role of physical exercise in functional reserve and capacity in relation to how we currently age. The regular practice of physical exercise provokes several favorable responses to the preservation of neuromuscular and cardiorespiratory function, which has a direct impact on physical capacity, even benefiting cognitive function. Physical exercise has been shown to have a protective effect on different systems, apart from contributing to the preservation of functionality and self-efficacy, which is why it is essential for healthy aging, since it favors a better resolution to stressful events such as falls and/or diseases. In conclusion, even though physical exercise does not prevent the deleterious conditions of aging, its effects are positively related to the maintenance of systemic functional reserve and capacity, which translates into greater autonomy, independence and quality of life related to health in the last stage of the life cycle.
... Occlusion training, defined as blood flow restriction training, has also shown an increase in diastolic and systolic blood pressure, heart rate, stroke volume, and cardiac output in older women (173). Endothelium-dependent vasodilation of skeletal muscle, angiogenic markers, and capillarity also show a positive response to flexibility training (174), which is a good alternative in older populations. High intensity exercise can lead to greater improvements in aerobic capacity and cardioprotective effect (175), in addition to endothelial function and quality of life (176), from which it is inferred that the exercise intensity can have an impact on its protective effect at the cardiovascular level and can be an important factor in maintaining and/or improving the aerobic capacity of older adults. ...
Aging is an inherent process to living beings that involves a deterioration of homeostatic regulation and functional reserve. Currently, the aging population has high levels of physical inactivity that aggravates muscle disuse, which in turn drastically affects functional capacity and quality of life. The aim of this narrative review is to present aging conditions and the protective role of physical exercise in functional reserve and capacity in relation to how we currently age. The regular practice of physical exercise provokes several favorable responses to the preservation of neuromuscular and cardiorespiratory function, which has a direct impact on physical capacity, even benefiting cognitive function. Physical exercise has been shown to have a protective effect on different systems, apart from contributing to the preservation of functionality and self-efficacy, which is why it is essential for healthy aging, since it favors a better resolution to stressful events such as falls and/or diseases. In conclusion, even though physical exercise does not prevent the deleterious conditions of aging, its effects are positively related to the maintenance of systemic functional reserve and capacity, which translates into greater autonomy, independence and quality of life related to health in the last stage of the life cycle.
... Prior work has shown that yoga (compared to brisk walking), practiced for 1 h per day, 6 days per week over 6 or 12 weeks, significantly reduced systolic blood pressure [3] and arterial stiffness [4] in elderly hypertensive participants. It is thought that yoga itself (through controlled breathing and relaxation) enables a reduction in the sympathetic innervation of the smooth muscle at the blood vessel [5], while others have postulated that the regular stretching that occurs with yoga may cause increased release and subsequent enhanced bioavailability of nitric oxide, causing endothelium-dependent decreased vasoconstrictor tone [6]. However, such acute studies rarely account for lifestyle factors (for example, leisure-time physical activity) or underlying metabolic conditions (e.g., prediabetes), and whether similar positive cardiovascular effects are evident in a healthy 2 of 8 population practicing yoga is yet to be determined. ...
Background:
Yoga may help adults of all fitness levels increase their physical activity and decrease their cardiovascular disease risk.
Aim:
To determine if arterial stiffness is lower (beneficial) in yoga versus non-yoga participants.
Method:
This cross-sectional study included 202 yoga (48.4 + 14.1 years, 81% female) and 181 (42.8 + 14.1 years, 44% female) non-yoga participants. The primary outcome was carotid-femoral pulse wave velocity (cfPWV). The two groups were compared using analysis of covariance with adjustments for demographic (age and sex), hemodynamic (mean arterial pressure and heart rate), lifestyle (physical activity levels, sedentary behaviour, smoking status and perceived stress score) and cardiometabolic (waist-to-hip ratio, total cholesterol and fasting glucose) factors.
Results:
Following adjustments, cfPWV was significantly lower in yoga compared to non-yoga participants with a mean difference: -0.28 m.s-1, (95% CI = -0.55 to 0.08).
Conclusion:
At a population level, yoga participation may assist with decreasing the risk of cardiovascular disease in adults.
... Thus, testing the FL alteration at lengthened position should be recommended being as a sensitive location for detecting some FL changes in response to stretching exercise. Impairment of endothelium-dependent vasodilation of resistant arteries was noticed to occur with age (Hotta et al., 2018). In the present study, a higher artery velocity baseline for older adults was found when compared with the young group. ...
Introduction:
The physiological and structural alterations have been less reported in response to dynamic stretching (DS) or neurodynamic nerve gliding (NG). Accordingly, this study investigated the changes in fascicle lengths (FL), popliteal artery velocity, and physical fitness in response to a single bout of DS or NG.
Methods:
The study included 15 healthy young adults (20.9 ± 0.7 yrs) and 15 older adults (66.6 ± 4.2 yrs) who randomly performed three different interventions (DS, NG, and rest control) for 10 min and 3 days apart. The biceps femoris and semitendinosus FL, popliteal artery velocity, sit and reach (S&R), straight leg raise (SLR), and fast walking speed were measured before and immediately after the intervention.
Results:
After NG intervention, S&R was largely greater by 2 cm (1.2, 2.8 cm) and 3.4 cm (2.1, 4.7 cm) with largely increased SLR angles of 4.9° (3.7°, 6.1°) and 4.6° (3.0°, 6.2°) with all p < 0.001 for the older adults and young groups, respectively. A similar magnitude improvement in the S&R and SLR testing was also seen for both groups after DS (p < 0.05). Moreover, no changes were seen in FL, popliteal artery velocity, fast gait speed, and age effect following all three intervention occasions.
Conclusion:
Stretching with DS or NG immediately increased flexibility, which appeared to be largely due to changes in stretch tolerance rather than an increase in fascicle length. Furthermore, age dependency in response to stretching exercise was not seen in the present study.
... Systemically, PA has shown to have a regulatory effect on inflammatory markers, and the different intervention training modes have different effects on neuroinflammatory cytokine [129][130][131] . Endothelial function was also improved after exercise [132][133] . Studies reported that PA may regulate Aβ and tau levels in mice model of AD, but consistency is poor in human groups [134] . ...
Alzheimer’s disease is a neurodegenerative disease with complex etiology. Gut microbiota influences the gut-brain axis, which may affect pathways related to the pathogenesis of Alzheimer’s disease. Additionally, diet and physical activity are likely to affect the pathology of Alzheimer’s disease as well as the gut microbiota. This demonstrates that it may be possible to prevent or halt the progression of Alzheimer’s disease by regulating the gut microbiota using diet and physical activity strategies. Therefore, the present study reviews the association between these two interventions and gut microbiota in the human body. It also summarizes how these two interventions benefit Alzheimer’s disease. Furthermore, the primary limitations of these two interventions are discussed and promising strategies are proposed, which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer’s disease.
... Flexibility refers to the range of motion (ROM) available within one or more articulations, allowing the execution of physiological movement (Hotta et al., 2018). Thus, the decrease in flexibility may interfere in daily life activities, increase the incidence of injury, and alter sports performance (Thomas, Bianco, Paoli, & Palma, 2018;Wang, Ikeda, & Ikoma, 2021;Xiao et al, 2020). ...
Background: Stretching is an effective strategy used mainly to reduce muscle stiffness, and increase both flexibility and Range of Motion. Aim: To compare the effects of different thermotherapy modalities associated with static stretching on peak torque (PT) of knee flexor muscles. Methods: This study compared a sample of 34 healthy men, aged between 20 and 30 years, with active knee range of motion (ROM) ≤160 degrees. They were subjected to three sessions of static stretching of the hamstrings, either with or without a thermotherapy modality. The order of interventions was randomized for one of the groups: isolated stretching (IS), stretching with heat (SH), and stretching with cold (SC). The concentric and eccentric PTs were assessed pre and post-intervention. Results: In the comparison of PT among different measures, there was a significant decrease in eccentric and concentric PT of knee flexor muscles in IS, in eccentric PT of knee flexor muscles in SH, and in eccentric and concentric PT of knee flexors in SC groups. Conclusion: Regardless of the use of thermotherapy, one single session of static stretching resulted in decreased PT of knee flexor muscles. This is probably due to the effects of stretching, such as the immediate change of the elastic component of the muscle-tendon unit, which leads to a deficit in acute force production.
The book focuses on a new interdisciplinary understanding of the metabolic syndrome (MetS) for better health maintenance. It provides an updated understanding of the underlying principles, possible targets, implementation approaches and the effectiveness of various avoidance strategies in MetS. The chapters cover a wide range of topics, including major advances in general aspects of metabolic syndrome, functional changes, new diagnostic methods, genotype-phenotype associations, the effect of exercise and multitarget pharmacotherapeutic strategies for MetS and perspectives on personalized medicine. It also discusses epigenetic mechanisms underlying MetS-related processes and epigenetic strategies to prevent related diseases. The book also presents summarized information about the associated factors and mechanisms linking cancer and MetS and to identify potential targets for the treatment of these patients. A better understanding of the various linkages will provide greater insight into the management of cancer patients by preventing MetS and related alterations. Key Features - Comprehensive information focused on the biological factors and physiological changes associated with metabolic syndrome - Updates on metabolic syndrome diagnosis and management - Summarized information on clinical implications for cancer therapy - Thoroughly referenced chapters with summaries and discussions for quick understanding The book is an informative resource for interdisciplinary scientists and researchers in life sciences and medicine. Furthermore, it, including the insulin-like growth factor (IGF-1) pathway, estrogen signaling, visceral adiposity, hyperinsulinemia, hyperglycemia, aromatase activity, adipokinase production, angiogenesis, oxidative stress, DNA damage and pro-inflammatory cytokines, and their clinical implications in cancer therapy.
Background
There are adverse effects on the health outcomes of workers whose occupation involves prolonged standing, such as lower back pain, leg pain, cardiovascular diseases, fatigue, discomfort, and pregnancy-related health outcomes. The effectiveness of massage therapy as an intervention for managing leg pain associated with prolonged standing needs to be addressed.
Aims
This study aimed to evaluate the smart dynamic fabric actuator’s effectiveness in treating chronic musculoskeletal leg pain in persons with occupations involving prolonged standing.
Setting
Tertiary care hospital.
Design
Randomized controlled trial.
Methods
Thirty participants with chronic leg pain satisfying the inclusion and exclusion criteria participated in the study. The intervention group used the device for 15 minutes for each leg once a day and stretching exercises twice a day for six weeks. The control group performed stretching exercises twice a day for six weeks. The outcome was assessed at baseline, three weeks, and six weeks with a Numeric Rating Scale for pain and fatigue, short form-McGill Pain Questionnaire for pain, and SF-36 for quality of life.
Statistical Analysis
The groups were compared using the two-sample t -test with equal variances, the two-sample Wilcoxon rank-sum test, and the Chi ² exact test as appropriate.
Results
Thirty medical (nursing officers and doctors) and nonmedical professionals (security guards and sales assistants) with a mean age of 32.9 ± 5.6 years (intervention group) and 36.2 ± 5.1 years (control group) participated in the study. At six weeks, a significant improvement in pain (4.80 ± 1.14 to 1.66 ± 1.04 vs 4.66 ± 0.89 to 2.6 ± 0.91, P = 0.014), quality of life (58.77 ± 9.06 to 71.76 ± 8.43 vs 51.39 ± 8.26 to 63.87 ± 7.61, P = 0.012), and reduced fatigue (5 to 2 vs 5 to 3, P = 0.003) was observed in the intervention group when compared with the control group. No adverse events were observed.
Conclusion
A smart dynamic fabric actuator can be used as an adjunct to exercises for reducing leg pain and fatigue associated with prolonged standing.
When recommending avoidance of static stretching prior to athletic performance, authors and practitioners commonly refer to available systematic reviews. However, effect sizes in previous reviews were in major parts extracted from studies lacking control conditions and/or pre-post testing designs. Also, currently available reviews conducted the calculations without accounting for multiple study outcomes, with effect sizes (ES)=-0.03 – 0.1 that would commonly be classified trivial. Since new meta-analytical software and controlled research articles arose since 2013, we revisited the available literature and performed a multilevel meta-analysis using robust variance estimation of controlled pre-post trials to provide updated evidence of the current state of literature. Furthermore, previous research described reduced EMG activity – also attributable to fatiguing training routines – as being responsible for decreased subsequent performance. The second part of this study opposed stretching and alternative interventions sufficient to induce general fatigue to examine if static stretching induces higher performance losses compared to other exercise routines. Including n=83 studies with more than 400 effect sizes from 2012 participants, our results indicate a significant, small ES for a static stretch-induced maximal strength loss (ES=-0.21, p=0.003), with high magnitude ES (ES=-0.84, p=0.004) for ≥60s stretching durations per bout when compared to passive controls. When opposed to active controls, the maximal strength loss ranges between ES=-0.17 – -0.28, p<0.001 – 0.04 with mostly no to small heterogeneity. However, stretching did not negatively influence athletic performance in general – neither when compared to passive nor active controls – while even a positive effect on subsequent jumping performance (ES=0.15, p=0.006) was found in adults. Regarding strength testing of isolated muscles (e.g., leg extensions or calf raises), our results confirm previous findings. Nevertheless, since no (or even positive) effects could be found for athletic performance, our results do not support previous recommendations to exclude static stretching from warm-up routines prior to, e.g., jumping or sprinting.
Background:
The local hemodynamic response after cupping therapy has been considered as a contributing factor for improving muscle tissue health; however, the effects of cupping pressure and duration on the spatial hemodynamic response have not been investigated.
Objective:
The objective of this study was to investigate the hemodynamic response inside and outside the cupping cup under various pressures and durations of cupping therapy.
Methods:
A 3-way factorial design with repeated measures was used to investigate the main and interaction effects of the location (areas inside and outside the cup), pressure (-225 and -300 mmHg) and duration (5 and 10 min) on the hemodynamic response of the biceps muscle. A functional near-infrared spectroscopy was used to assess hemodynamic changes in 18 participants.
Results:
A significant three-way interaction of the location, pressure, and duration factors was observed in oxyhemoglobin (p= 0.023), deoxy-hemoglobin (p= 0.013), and blood volume (p= 0.013). A significant increase was observed in oxyhemoglobin, blood volume, and oxygenation compared to pre-cupping (p< 0.05) in the area outside the cup.
Conclusion:
Our findings indicate that an appropriate combination of cupping pressure and duration can effectively affect the spatial hemodynamic response of the biceps.
AIM: Static stretching (SS) exercises are frequently used to increase muscle flexibility, improve physical performance, and reduce musculoskeletal injuries. The purpose of this study was to examine the acute effects of different SS duration applied to the gastrocnemius muscle on muscle blood flow by superb microvascular imaging (SMI) method and compare the impact of stretching at different duration immediately after stretching and 10 minutes later. MATERIAL AND METHOD: 30 healthy volunteers aged between 18-35 years were included in this study. The individuals were divided into two groups randomly. 2-minute SS was applied to the gastrocnemius muscle of the first group, and 5-minute SS was performed to the gastrocnemius muscle of the second group. Blood flow in the muscle after stretching was evaluated by the SMI method. RESULTS: It was obtained that muscle blood flow raised as a result of stretching applications for 2 minutes and 5 minutes, stretching application for 5 minutes increased blood flow more than stretching application for 2 minutes (p0.05). CONCLUSION: It was thought that 2 or 5 minutes of stretching applications to increase circulation in healthy individuals might be sufficient.
Purpose: Acute (immediate) or regular (mid- or long-term) stretching increases arterial compliance and reduces arterial stiffness. Stretching is widely known to induce arterial functional factor changes, but it is unclear whether stretching alters arterial structural factors. Ultrasound shear wave elastography can quantify the distribution of tissue elastic properties as an index of arterial structural factors. This study thus aimed to examine the effects of acute cervical stretching on arterial wall tissue elastic properties.
Methods: Seventeen healthy young adults participated in two different trials for 15 min in random order on separate days: a resting and sitting trial (CON) and a supervised cervical stretching trial (CS). In CS, subjects performed 10 different stretches. At each site, the stretch was held for 30 s followed by a 10-s relaxation period. In CON, subjects rested on a chair for 15 min.
Results: After the experiment, carotid arterial compliance, assessed by combined ultrasound imaging and applanation tonometry, was significantly increased in CS, but not in CON. However, there was no significant change in tissue elasticity properties of the arterial wall in either trial, as assessed by ultrasound shear wave elastography.
Conclusion: Acute cervical stretching significantly increased carotid artery compliance in young participants, but did not reduce elastic tissue properties (i.e., arterial structural factors) of the carotid artery wall. These results strongly suggest that changes in structural factors have little relation to stretching-induced acute increases in arterial compliance.
BACKGROUND:
As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres.
METHODS:
Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity.
RESULTS:
There was no significant age-related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people.
CONCLUSIONS:
The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age-related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing.
Background:
As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres.
Methods:
Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity.
Results:
There was no significant age-related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people.
Conclusions:
The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age-related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing.
Objectives Being physically active is important for health, and few Mexican-Americans meet national US physical activity recommendations. The aim of this study was to investigate sociodemographic, acculturation and lifestyle factors that were associated with meeting physical activity recommendations in this group.
Design and setting A cross-sectional analysis of a large population-based cohort study in southern Texas, USA.
Participants Between 2001 and 2011, 21 551 adult members of the Mexican-American Mano A Mano cohort completed baseline questionnaires on physical activity and other lifestyle factors.
Outcomes Meeting US physical activity recommendations was defined as participating in 150 min of moderate, or 75 min of vigorous, activity per week. Factors contributing to the likelihood of meeting physical activity recommendations were examined by sex and country of birth in multivariate logistic regression models.
Results Less than half of all men and less than a quarter of all women met US physical activity recommendations. Having some college education, greater acculturation and current alcohol use were each associated with greater odds of meeting physical activity recommendations in all groups except US-born men. Higher body mass index was associated with lower odds of meeting recommendations in US-born and Mexico-born women.
Conclusions Results demonstrate that factors associated with meeting physical activity recommendations differ by sex and country of birth. Tailored interventions to increase Mexican-Americans’ activity levels to achieve health benefits should consider education, acculturation and alcohol use.
Stretching exercises to increase the range of motion (ROM) of joints have been used by sports coaches and medical professionals for improving performance and rehabilitation. The ability of connective and muscular tissues to change their architecture in response to stretching is important for their proper function, repair, and performance. Given the dearth of relevant data in the literature, this review examined two key elements of stretching: stretch intensity and stretch position; and their significance to ROM, delayed onset muscle soreness (DOMS), and inflammation in different populations. A search of three databases, Pub-Med, Google Scholar, and Cochrane Reviews, identified 152 articles, which were subsequently categorized into four groups: athletes (24), clinical (29), elderly (12), and general population (87). The use of different populations facilitated a wider examination of the stretching components and their effects. All 152 articles incorporated information regarding duration, frequency and stretch position, whereas only 79 referred to the intensity of stretching and 22 of these 79 studies were deemed high quality. It appears that the intensity of stretching is relatively under-researched, and the importance of body position and its influence on stretch intensity, is largely unknown. In conclusion, this review has highlighted areas for future research, including stretch intensity and position and their effect on musculo-tendinous tissue, in relation to the sensation of pain, delayed onset muscle soreness, inflammation, as well as muscle health and performance.
Whether aging lowers skeletal muscle basal capillarization and angiogenesis remains controversial. To investigate the effects
of aging on skeletal muscle capillarization, eight young (YW) and eight aged (AW) women completed 8 weeks of exercise training.
The response and relationships of muscle capillarization, interstitial vascular endothelial growth factor (VEGF), and microvascular
blood flow to aerobic exercise training were investigated. Vastus lateralis biopsies were obtained before and after exercise
training for the measurement of capillarization. Muscle interstitial VEGF protein and microvascular blood flow were measured
at rest and during submaximal exercise at PRE, 1-WK, and 8-WKS by microdialysis. Exercise training increased (20%–25%) capillary
contacts of type I, IIA, and IIB fibers in YW and AW. Interstitial VEGF protein was higher in AW than YW at rest and was higher
in YW than AW during exercise independent of training status. Differences in muscle capillarization were not explained by
secreted VEGF nor were differences in VEGF explained by microvascular blood flow. These results confirm that aging (57–76
years age range) does not impair the muscle angiogenic response to exercise training, although sex differences may exist in
similarly trained women and men.
Exercise training ameliorates age-related impairments in endothelium-dependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained (ET) or remained sedentary (SED) for 10 wks. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine (ACh) were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with Tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or GPx1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and GPx1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise training-induced enhancement of endothelial function occurs in part through an increase in ROS signaling.
With old age there is reduced blood flow during exercise to the high-oxidative red skeletal muscle and elevated flow to the low-oxidative white muscle. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypotheses that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6-7 mo old; n=36) and old (24 mo old; n=25) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise-trained (YET) or old exercise-trained (OET) groups, where training consisted of 10-12 weeks of treadmill exercise. In Sed and ET rats blood flow at rest and during exercise to the red and white portions of the gastrocnemius muscle (Gast(Red) and Gast(White), respectively), and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured. In the old ET group, blood flow was greater to the Gast(Red) (OET: 264 ± 13, OSed: 195 ± 9 ml/min/100 g) and lower to the Gast(White) (OET: 78 ± 5, OSed: 120 ± 6 ml/min/100 g) during exercise versus OSed. There was no difference in the number of feed arteries in OET versus OSed, although feed arteries from OET rats had a larger CSA. In YET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by ET with old age would improve the local matching of O(2) delivery-to-consumption within the skeletal muscle.
Muscle microvascularization is usually quantified in transverse sections, in absolute terms (capillaries around fibres, CAF, or capillary-to-fibre ratio, C/F) or as CAF related to fibre area (CAF/area, CAFA). The capillary-to-fibre perimeter exchange ratio (CFPE) has been introduced in order to assess the role of the capillary-to-fibre interface in resistance to O(2) diffusion. The ratio between the length of capillaries in contact with fibres and fibre perimeter (LC/PF) has also been used as an index for capillary tortuosity. The possibility of change in capillary tortuosity with endurance training was not considered in previous studies. Consequently, this study investigated the effect of 14 weeks of endurance training on muscle microvascularization, including microvessel tortuosity, in 11 elderly men (8th decade). Microvessels were analysed using the CD31 antibody. Together with the significant increase in peak oxygen exchange and citrate synthase activity, there was a significant increase in C/F. While CFPE and CAFA remained unchanged, an important finding was the clear increase in LC/PF (56%; P < 0.001) for a same sarcomere length. We also found a strong correlation between oxidative enzyme activity and LC/PF both before and after training. These results indicate that endurance training induces significant remodelling in the microvessel network in elderly men and that an increase in the degree of microvessel tortuosity would be an important mechanism of adaptation to endurance training.
Although a multitude of factors that influence skeletal muscle blood flow have been extensively investigated, the influence of muscle length on limb blood flow has received little attention. Thus the purpose of this investigation was to determine if cyclic changes in muscle length influence resting blood flow. Nine healthy men (28 ± 4 yr of age) underwent a passive knee extension protocol during which the subjects' knee joint was passively extended and flexed through 100-180° knee joint angle at a rate of 1 cycle per 30 s. Femoral blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), and mean arterial pressure (MAP) were continuously recorded during the entire protocol. These measurements revealed that slow passive changes in knee joint angle did not have a significant influence on HR, SV, MAP, or CO; however, net femoral blood flow demonstrated a curvilinear increase with knee joint angle (r(2) = 0.98) such that blood flow increased by ∼90% (125 ml/min) across the 80° range of motion. This net change in blood flow was due to a constant antegrade blood flow across knee joint angle and negative relationship between retrograde blood flow and knee joint angle (r(2) = 0.98). Thus, despite the absence of central hemodynamic changes and local metabolic factors, blood flow to the leg was altered by changes in muscle length. Therefore, when designing research protocols, researchers need to be cognizant of the fact that joint angle, and ultimately muscle length, influence limb blood flow.
The contribution of neuronal nitric oxide synthase (nNOS) to angiogenesis in human skeletal muscle after endurance exercise is controversially discussed. We therefore ascertained whether the expression of nNOS is associated with the capillary density in biopsies of the vastus lateralis (VL) muscle that had been derived from 10 sedentary male subjects before and after moderate training (four 30-min weekly jogging sessions for 6 months, with a heart-rate corresponding to 75% VO(2)max). In these biopsies, nNOS was predominantly expressed as alpha-isoform with exon-mu and to a lesser extent without exon-mu, as determined by RT-PCR. The mRNA levels of nNOS were quantified by real-time PCR and related to the capillary-to-fibre ratio and the numerical density of capillaries specified by light microscopy. If the VL biopsies of all subjects were co-analysed, mRNA levels of nNOS were non-significantly elevated after training (+34%; P > 0.05). However, only five of the ten subjects exhibited significant (P ≤ 0.05) elevations in the capillary-to-fibre ratio (+25%) and the numerical density of capillaries (+21%) and were thus undergoing angiogenesis. If the VL biopsies of these five subjects alone were evaluated, the mRNA levels of nNOS were significantly up-regulated (+128%; P ≤ 0.05) and correlated positively (r = 0.8; P ≤ 0.01) to angiogenesis. Accordingly, nNOS protein expression in VL biopsies quantified by immunoblotting was significantly increased (+82%; P ≤ 0.05) only in those subjects that underwent angiogenesis. In conclusion, the expression of nNOS at mRNA and protein levels was statistically linked to capillarity after exercise suggesting that nNOS is involved in the angiogenic response to training in human skeletal muscle.
Vascular endothelial growth factor (VEGF), a potent angiogenic factor and endothelial cell-specific mitogen, is up-regulated
by hypoxia. However, the mechanism(s) responsible for hypoxic induction of VEGF has not been clearly delineated. We report
that the steady state VEGF mRNA levels are increased 12 ± 0.6-fold, but the transcriptional rate for VEGF is increased only
3.1 ± 0.6-fold by hypoxia in PC12 cells. In order to investigate cis-regulatory sequences which mediate this response to hypoxia, we cloned the rat genomic sequences encoding VEGF and identified
a 28-base pair element in the 5′ promoter that mediates hypoxia-inducible transcription in transient expression assays. This
element has sequence and protein binding similarities to the hypoxia-inducible factor 1 binding site within the erythropoietin
3′ enhancer. Post-transcriptional mechanisms have also been suggested to play a role in the hypoxic induction of VEGF. Evidence
is provided that a frequently used polyadenylation site is 1.9 kilobases downstream from the translation termination codon
for rat VEGF. This site is 1.5 kilobases further downstream from the polyadenylation site previously reported for VEGF. This
new finding reveals sequence motifs in the 3′-untranslated region that may mediate VEGF mRNA stability.
Expression of vascular endothelial growth factor (VEGF) is induced in cells exposed to hypoxia or ischemia. Neovascularization stimulated by VEGF occurs in several important clinical contexts, including myocardial ischemia, retinal disease, and tumor growth. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein that activates transcription of the human erythropoietin gene in hypoxic cells. Here we demonstrate the involvement of HIF-1 in the activation of VEGF transcription. VEGF 5'-flanking sequences mediated transcriptional activation of reporter gene expression in hypoxic Hep3B cells. A 47-bp sequence located 985 to 939 bp 5' to the VEGF transcription initiation site mediated hypoxia-inducible reporter gene expression directed by a simian virus 40 promoter element that was otherwise minimally responsive to hypoxia. When reporters containing VEGF sequences, in the context of the native VEGF or heterologous simian virus 40 promoter, were cotransfected with expression vectors encoding HIF-1alpha and HIF-1beta (ARNT [aryl hydrocarbon receptor nuclear translocator]), reporter gene transcription was much greater in both hypoxic and nonhypoxic cells than in cells transfected with the reporter alone. A HIF-1 binding site was demonstrated in the 47-bp hypoxia response element, and a 3-bp substitution eliminated the ability of the element to bind HIF-1 and to activate transcription in response to hypoxia and/or recombinant HIF-1. Cotransfection of cells with an expression vector encoding a dominant negative form of HIF-1alpha inhibited the activation of reporter transcription in hypoxic cells in a dose-dependent manner. VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells.
As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 ± 0.05 to 3.13 ± 0.11 μm. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 μm, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 ± 0.03 μm at 2.4-2.6 μm sarcomere length to 4.12 ± 0.05 μm at 3.2-3.4 μm sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased ~40% from 24.3 ± 7.5 to 14.5 ± 4.6 ml·100 g-1·min-1 . The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 ± 0.6% at the shortest sarcomere lengths to 56.5 ± 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.
The purpose of this study was to determine the effects of aging on the distribution of cardiac output (Q), tissue blood flow (BF) and body composition in juvenile (J, 2 months old), adult (A, 6 months old) and old (O, 24 months old) male Fischer-344 rat. Q was lower in J rats (51 ± 4 ml · min-1) than in A (106 ± 5) or O (119 ± 10) rats, but cardiac index was not different among groups. The proportion of Q going to most tissues did not change with increasing age. However, the fraction of Q to brain and skeletal muscle was greater in J rats than in the A and O groups. O rats had a greater percent Q to fat and a lower percent Q to cutaneous and reproductive tissues than in J or A rats. Age also had little effect on mass specific BF in most tissues. However, J rats had lower BF to the pancreas, GI tract, thyroid gland and kidneys than did A rats, and O rats had lower BF to rectus femoris muscle, spleen, thyroid gland and prostate gland than did A rats. Body mass of J rats was composed of a lower percent adipose mass and a greater fraction of brain, heart, kidney, liver and skeletal muscle than that in the A and O animals. Relative to the A rats, the body mass of O animals had a greater percent fat mass and a lower percent muscle and skin mass. These data demonstrate that aging has a significant effect on the distribution of Q and body composition, but relatively little influence on mass specific tissue BF in conscious rats.
mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1alpha and HIF-1beta in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (approximately 15-20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1beta by 340%, but not HIF-1alpha and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1alpha and HIF-1beta mRNA. The changes in VEGF, HIF-1alpha, and HIF-1beta mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1alpha and HIF-1beta mRNA.
Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(1) (TGF-beta(1)) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF-beta(1) gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups (n = 6 each): 1) saline + rest, 2) saline + exercise, 3) 30 mg/kg N(omega)-nitro-L-arginine methyl ester (L-NAME, a known NOS inhibitor) + rest, 4) 30 mg/kg L-NAME + exercise, 5) 300 mg/kg L-NAME + rest, 6) 300 mg/kg L-NAME + exercise, 7) 300 mg/kg N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive enantiomer of L-NAME) + rest, and 8) 300 mg/kg D-NAME + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF-beta(1) mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated approximately 50% by 30 and 300 mg/kg L-NAME; the TGF-beta(1) mRNA increase was unaffected by 300 mg/kg L-NAME. In addition, 300 mg/kg D-NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg L-NAME had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life.
To investigate the hypothesis that capillary proliferation in skeletal muscles, induced by a long-term increase in blood flow which elevates capillary shear stress, is associated with capillary expression of vascular endothelial growth factor (VEGF).
Adult rats received prazosin in drinking water ( approximately 2 mg per day) or had extensor digitorum longus (EDL) muscles stimulated by implanted electrodes for up to 14 days. At intervals, serial frozen sections of EDL were stained for alkaline phosphatase to identify capillaries, proliferating cell nuclear antigen (PCNA), and VEGF-A protein. Shear stress was estimated from capillary red blood cell velocities and diameters, measured by direct observation of epi-illuminated EDL.
Chronic stimulation and prazosin treatment both increased capillary: fiber ratio by approximately 40% after 14 days. In stimulated muscles, the percentage of capillaries positively stained for VEGF increased within 3 to 4 days, while the density of PCNA-positive capillaries had increased 20-fold after 2 days. With prazosin, VEGF-positive capillaries increased after 2 and 4 days, accompanied by a threefold increase in PCNA. By 14 days, PCNA labeling and VEGF were still high in stimulated muscles, but no longer different from controls with prazosin. After 3 to 4 days of treatment, capillary shear stress in resting muscle was 57% higher than in controls as a result of stimulation, but 4 times higher with prazosin.
Higher capillary shear stress with prazosin than with stimulation may upregulate VEGF expression in the early stages of treatment. Greater proliferation of capillaries preceding a higher proportion of VEGF-positive capillaries in stimulated muscles, in the presence of a modest increase in shear stress, suggests that angiogenesis was initiated by other factors in addition to shear stress.
Blood flow capacity in skeletal muscle declines with age. Reduced blood flow capacity may be related to decline in the maximal vasodilatory capacity of the resistance vasculature. This study tested the hypothesis that aging results in impaired vasodilatory capacity of first-order (1A) arterioles isolated from rat-hindlimb locomotory muscle: 1A arterioles (90-220 microm) from gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-144 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasodilatory responses to increasing concentrations of ACh (10(-9) to 10(-4) M), adenosine (ADO, 10(-10) to 10(-4) M), and sodium nitroprusside (SNP, 10(-10) to 10(-4) M) were evaluated at a constant intraluminal pressure of 60 cmH(2)O in the absence of flow. Flow-induced vasodilation was also evaluated in the absence of pressure changes. Responses to ADO and SNP were not altered by age. Endothelium-dependent vasodilation induced by flow was significantly reduced in arterioles from both gastrocnemius and soleus muscles. In contrast, endothelium-dependent vasodilation to ACh was reduced only in soleus muscle arterioles. These results indicate that aging impairs vasodilatory responses mediated through the endothelium of resistance arterioles from locomotory muscle, whereas smooth muscle vasodilatory responses remain intact with aging. Additionally, ACh-induced vasodilation was altered by age only in soleus muscle arterioles, suggesting that the mechanism of age-related endothelial impairment differs in arterioles from soleus and gastrocnemius muscles.
Capillary growth in skeletal muscle occurs via the dissimilar processes of abluminal sprouting or longitudinal splitting, which can be initiated by muscle stretch and elevated shear stress, respectively. The distinct morphological hallmarks of these types of capillary growth suggest that discrete sets of angiogenic mediators play a role in each situation. Because proteolysis and proliferation are two key steps associated with capillary growth, we tested whether differences in the regulation of matrix metalloproteinases (MMPs) or VEGF may be associated with the two types of capillary growth. We found significant increases in MMP-2 total protein and percent activation, and membrane type-1 MMP mRNA levels, compared with controls after muscle stretch but not after shear stress stimulation. In contrast, VEGF protein and endothelial cell proliferation increased after either angiogenic stimulus. We observed that MMP-2 regulation occurs independent of VEGF signaling, because VEGF did not induce MMP-2 production or activation in isolated endothelial cells. Our data suggest that the involvement of MMPs in capillary growth is dependent on the nature of the angiogenic stimulus.
Maximal aerobic capacity and the ability to sustain submaximal exercise (Ex) declines with advancing age. Whether altered muscle blood flow (BF) plays a mechanistic role in these effects remains to be resolved. The present investigation determined the effects of aging on the hemodynamic and regional BF response to submaximal Ex in rats. Heart rate (HR), mean arterial pressure (MAP), and BF to different organs (kidneys, splanchnic organs, and 28 hindlimb muscles) were determined at rest and during submaximal treadmill Ex (20 m/min, 5% grade) with radiolabeled microspheres in young (Y; 6-8 mo old, 339 +/- 8 g, n = 9) and old (O; 27-29 mo old, 504 +/- 18 g, n = 7) Fischer 344 x Brown Norway rats. Results demonstrated that HR, MAP, and BF to the pancreas, small and large intestine, and total hindlimb musculature were similar between Y and O rats at rest. BF to the kidneys, spleen, and stomach were 33, 60, and 43% lower, respectively, in O compared with Y rats. BF to the total hindlimb musculature increased (P < 0.05) during Ex and was similar for both Y and O rats (Y: 16 +/- 3 to 124 +/- 7 vs. O: 20 +/- 3 to 137 +/- 12 ml.min-1.100 g-1). However, in O vs. Y rats, BF was reduced in 6 (highly oxidative) and elevated in 8 (highly glycolytic) of the 28 individual hindquarter muscles or muscle parts examined (P < 0.05). During Ex, BF to the spleen and stomach decreased (P < 0.05) from rest in Y rats, whereas BF decreased in the kidneys, pancreas, spleen, stomach, as well as the small and large intestines of O rats. In conclusion, these data demonstrate that, despite similar increases in total hindlimb BF in Y and O rats during submaximal Ex, there is a profound BF redistribution from highly oxidative to highly glycolytic muscles.
The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia is thus a critical parameter in muscle function, influencing production of ATP, utilization of energy-producing substrates, and manufacture of exhaustion-inducing metabolites. Glycolysis is the central source of anaerobic energy in animals, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). To determine the role of HIF-1alpha in regulating skeletal muscle function, we tissue-specifically deleted the gene encoding the factor in skeletal muscle. Significant exercise-induced changes in expression of genes are decreased or absent in the skeletal-muscle HIF-1alpha knockout mice (HIF-1alpha KOs); changes in activities of glycolytic enzymes are seen as well. There is an increase in activity of rate-limiting enzymes of the mitochondria in the muscles of HIF-1alpha KOs, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway. This is corroborated by a finding of no significant decreases in muscle ATP, but significantly decreased amounts of lactate in the serum of exercising HIF-1alpha KOs. This metabolic shift away from glycolysis and toward oxidation has the consequence of increasing exercise times in the HIF-1alpha KOs. However, repeated exercise trials give rise to extensive muscle damage in HIF-1alpha KOs, ultimately resulting in greatly reduced exercise times relative to wild-type animals. The muscle damage seen is similar to that detected in humans in diseases caused by deficiencies in skeletal muscle glycogenolysis and glycolysis. Thus, these results demonstrate an important role for the HIF-1 pathway in the metabolic control of muscle function.
Therapeutic angiogenesis provides a potential alternative for the treatment of cardiovascular ischemic diseases. Vascular endothelial growth factor (VEGF) is an important component of the angiogenic response to ischemia. Here we used adeno-associated virus (AAV) gene delivery to skeletal muscle to examine the effects of VEGF vs. a stabilized form of hypoxia-inducible factor-1alpha (HIF-1alpha). The recombinant AAVs were injected into mouse tibialis anterior muscle, and their effects were analyzed by immunohistochemistry and functional assays. These analyses showed that stabilized HIF-1alpha markedly increase capillary sprouting and proliferation, whereas VEGF164 or VEGF120 induced only proliferation of endothelial cells without formation of proper capillary structures. The Evans Blue permeability assay indicated that, unlike VEGF, HIF-1alpha overexpression did not increase vascular leakiness in the transduced muscle. Doppler ultrasound imaging showed that vascular perfusion in the HIF-1alpha treated muscles was significantly enhanced when compared to the controls and not further improved by co-expression of the arteriogenic growth factors angiopoietin-1 or platelet-derived growth factor-B. Our results show that AAV-mediated transduction of a stabilized form of HIF-1alpha can circumvent the problems associated with overexpression of individual angiogenic growth factors. HIF-1alpha should thus offer a potent alternative for pro-angiogenic gene therapy.
Vascular endothelial growth factor (VEGF), a potent angiogenic factor and endothelial cell-specific mitogen, is up-regulated by hypoxia. However, the mechanism(s) responsible for hypoxic induction of VEGF has not been clearly delineated. We report that the steady state VEGF mRNA levels are increased 12 +/- 0.6-fold, but the transcriptional rate for VEGF is increased only 3.1 +/- O.6-fold by hypoxia in PC12 cells. In order to investigate cis-regulatory sequences which mediate this response to hypoxia, we cloned the rat genomic sequences encoding VEGF and identified a 28-base pair element in the 5' promoter that mediates hypoxia-inducible transcription in transient expression assays. This element has sequence and protein binding similarities to the hypoxia-inducible factor 1 binding site within the erythropoietin 3' enhancer. Post-transcriptional mechanisms have also been suggested to play a role in the hypoxic induction of VEGF. Evidence is provided that a frequently used polyadenylation site is 1.9 kilobases downstream from the translation termination codon for rat VEGF. This site is 1.5 kilobases further downstream from the polyadenylation site previously reported for VEGF. This new finding reveals sequence motifs in the 3'-untranslated region that may mediate VEGF mRNA stability.
Background: Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Objective: To compare muscle fiber type specific capillary density and endothelial function between healthy young, older men and age-matched type 2 diabetes patients. Design: 15 healthy young men (24±1 y), 15 healthy older men (70±2 y), and 15 age-matched type 2 diabetes patients (70±1 y) were selected to participate in the present study. Whole-body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density and dimension of the erythrocyte perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Results: Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Conclusions: Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.
The purpose of this study was to clarify the acute effects of a single session of stretching exercises on vascular endothelial function and peripheral circulation in patients with acute myocardial infarction. This study evaluated 32 patients (mean age, 66 ± 9 years) who received phase I cardiac rehabilitation after acute myocardial infarction. Five types of stretching exercises were performed on the floor: wrist dorsiflexion, close-legged trunk flexion, open-legged trunk flexion, open-legged lateral trunk bending, and cross-legged trunk flexion. Each exercise entailed a 30-second stretching followed by a 30-second relaxation, and was repeated twice. Low- and high-frequency components (LF and HF) of heart rate variability (LF, 0.04-0.15 Hz; HF, 0.15-0.40 Hz) were analyzed, and HF and LF/HF were used as indices of parasympathetic and sympathetic nervous activities, respectively. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index was measured and used as a parameter for vascular endothelial function. Transcutaneous oxygen pressure (tcPO2) on the right foot and chest was also measured, and the Foot-tcPO2/Chest-tcPO2 ratio was used as a parameter for peripheral circulation. The HF, RH-PAT index, and Foot-tcPO2/Chest-tcPO2 ratio were significantly higher after the exercises than before (P < 0.05, P < 0.01, and P < 0.05, respectively). There was no significant difference in the LF/HF ratio measured before and after stretching exercises. These findings demonstrate that stretching exercises improve vascular endothelial function and peripheral circulation in patients with acute myocardial infarction.
With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O(2) delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O(2) delivery to O(2) uptake, evidenced through improved microvascular Po(2) (Pm(O(2))), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify Pm(O(2)) in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline Pm(O(2)) (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting Pm(O(2)) and the time-delay before Pm(O(2)) fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the Pm(O(2)) in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.
Background:
Contractures are a disabling complication of neurological conditions that are commonly managed with stretch.
Objective:
The purpose of this systematic review was to determine the effectiveness of stretch for the treatment and prevention of contractures. The review is part of a more-detailed Cochrane review. Only the results of the studies including patients with neurological conditions are reported here.
Data sources:
Electronic searches were conducted in June 2010 in the following computerized databases: Cochrane CENTRAL Register of Controlled Trials, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, SCI-EXPANDED, and Physiotherapy Evidence Database (PEDro).
Study eligibility criteria:
The review included randomized controlled trials and controlled clinical trials of stretch applied for the purposes of treating or preventing contractures in people with neurological conditions.
Study appraisal and synthesis methods:
Two reviewers independently selected studies, extracted data, and assessed risk of bias. The primary outcome measures were joint mobility (range of motion) and quality of life. Secondary outcome measures were pain, spasticity, activity limitation, and participation restriction. Meta-analyses were conducted using random-effects models.
Results:
Twenty-five studies met the inclusion criteria. These studies provide moderate-quality evidence that stretch has a small immediate effect on joint mobility (mean difference=3°, 95% confidence interval [CI]=0° to 5°) and high-quality evidence that stretch has little or no short-term or long-term effects on joint mobility (mean difference=1° and 0°, respectively, 95% CI=0° to 3° and -2° to 2°, respectively). There is little or no effect of stretch on pain, spasticity, and activity limitation.
Limitations:
No studies were retrieved that investigated the effects of stretch for longer than 6 months.
Conclusion:
Regular stretch does not produce clinically important changes in joint mobility, pain, spasticity, or activity limitation in people with neurological conditions.
Background:
Decreased venous tone and vein wall dilation may contribute to varicose vein formation. We have shown that prolonged vein wall stretch is associated with upregulation of matrix metalloproteases (MMPs) and decreased contraction. Because hypoxia-inducible factors (HIFs) expression also increases with mechanical stretch, this study tested whether upregulation of HIFs is an intermediary mechanism linking prolonged vein wall stretch to the changes in MMP expression and venous contraction.
Methods:
Segments of rat inferior vena cava (IVC) were suspended in tissue bath under 0.5-g basal tension for 1 hour, and a control contraction to phenylephrine (PHE, 10(-5)M) and KCl (96 mM) was elicited. The veins were then exposed to prolonged 18 hours of tension at 0.5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethylamino)ethyl] amino-17-desmethoxygeldanamycin (17-DMAG, 10(-5)M), or echinomycin (10(-6)M), or 2 g plus dimethyloxallyl glycine (DMOG; 10(-4)M), a prolyl-hydroxylase inhibitor that stabilizes HIF. The fold-change in PHE and KCl contraction was compared with the control contraction at 0.5-g tension for 1 hour. Vein tissue homogenates were analyzed for HIF-1α, HIF-2α, MMP-2, and MMP-9 messenger RNA (mRNA) and protein amount using real-time reverse transcription polymerase chain reaction and Western blots.
Results:
Compared with control IVC contraction at 0.5-g tension for 1 hour, the PHE and KCl contraction after prolonged 0.5-g tension was 2.0 ± 0.35 and 1.1 ± 0.06, respectively. Vein contraction to PHE and KCl after prolonged 2-g tension was significantly reduced (0.87 ± 0.13 and 0.72 ± 0.05, respectively). PHE-induced contraction was restored in IVC exposed to prolonged 2-g tension plus the HIF inhibitor U0126 (1.38 ± 0.15) or echinomycin (1.99 ± 0.40). U0126 and echinomycin also restored KCl-induced contraction in IVC exposed to prolonged 2-g tension (1.14 ± 0.05 and 1.11 ± 0.15, respectively). Treatment with DMOG further reduced PHE- and KCl-induced contraction in veins subjected to prolonged 2-g tension (0.47 ± 0.06 and 0.57 ± 0.01, respectively). HIF-1α and HIF-2α mRNA were overexpressed in IVC exposed to prolonged 2-g tension, and the overexpression was reversed by U0126. The overexpression of HIF-1α and HIF-2α in stretched IVC was associated with increased MMP-2 and MMP-9 mRNA. The protein amount of HIF-1α, HIF-2α, MMP-2, and MMP-9 was also increased in IVC exposed to prolonged 2-g wall tension.
Conclusions:
Prolonged increases in vein wall tension are associated with overexpression of HIF-1α and HIF-2α, increased MMP-2 and MMP-9 expression, and reduced venous contraction in rat IVC. Together with our report that MMP-2 and MMP-9 inhibit IVC contraction, the data suggest that increased vein wall tension induces HIF overexpression and causes an increase in MMP expression and reduction of venous contraction, leading to progressive venous dilation and varicose vein formation.
Vascular endothelial cells (ECs) play a central role in the control of blood vessel function and circulatory system homeostasis. It is well known that that EC functions are regulated by chemical mediators, including hormones, cytokines, and neurotransmitters, but it has recently become apparent that EC functions are also controlled by hemodynamic forces such as shear stress and stretch (cyclic strain). ECs recognize shear stress and cyclic strain as mechanical stimuli, and transmit the signal into the interior of the cells, thereby triggering a variety of cellular responses that involve alterations in cell morphology, cell function, and gene expression. Impaired EC responses to shear stress and cyclic strain lead to vascular diseases, including hypertension, thrombosis, and atherosclerosis. A great deal of research has already been conducted on the mechanotransduction of shear stress and cyclic strain, and its molecular mechanisms are gradually coming to be understood. However, much remains unclear, and further studies of mechanotransduction should increase our understanding of the molecular basis of the hemodynamic-force-mediated control of vascular functions.
To determine whether objectively measured physical activity levels are associated with physical function and mobility in older men.
Cross-sectional.
Academic research center.
Eighty-two community-dwelling men aged 65 and older with self-reported mobility limitations were divided into a low-activity and a high-activity group based on the median average daily physical activity counts of the whole sample.
Physical activity according to triaxial accelerometers; physical function and mobility according to the Short Physical Performance Battery (SPPB), gait speed, stair climb time, and a lift-and-lower task; aerobic capacity according to maximum oxygen consumption (VO(2) max); and leg press and chest press maximal strength and peak power.
Older men with higher physical activity levels had a 1.4-point higher mean SPPB score and a 0.35-m/s faster walking speed than those with lower physical activity levels. They also climbed a standard flight of stairs 1.85 seconds faster and completed 60% more shelves in a lift-and-lower task (all P<.01); muscle strength and power measures were not significantly different between the low- and high-activity groups. Correlation analyses and multiple linear regression models showed that physical activity is positively associated with all physical function and mobility measures, leg press strength, and VO(2) max.
Older men with higher physical activity levels demonstrate better physical function and mobility than their less-active peers. Moreover, physical activity levels are predictive of performance in measures of physical function and mobility in older men. Future work is needed to determine whether modifications in physical activity levels can improve or preserve physical performance in later life.
The effect of a period of passive movement training on angiogenic factors and capillarization in skeletal muscle was examined. Seven young males were subjected to passive training for 90 min, four times per week in a motor-driven knee extensor device that extended one knee passively at 80 cycles min₋₁. The other leg was used as control. Muscle biopsies were obtained from m. v. lateralis of both legs before as well as after 2 and 4 weeks of training. After the training period, passive movement and active exercise were performed with both legs, and muscle interstitial fluid was sampled from microdialysis probes in the thigh. After 2 weeks of training there was a 2-fold higher level of Ki-67 positive cells, co-localized with endothelial cells, in the passively trained leg which was paralleled by an increase in the number of capillaries around a fibre (P <0.05). Capillary density was higher than pre-training at 4 weeks of training (P <0.05). The training induced an increase in the mRNA level of endothelial nitric oxide synthase (eNOS), the angiopoietin receptor Tie-2 and matrix metalloproteinase (MMP)-9 in the passively trained leg and MMP-2 and tissue inhibitor of MMP (TIMP)-1 mRNA were elevated in both legs. Acute passive movement increased (P <0.05) muscle interstitial vascular endothelial growth factor (VEGF) levels 4- to 6-fold above rest and the proliferative effect, determined in vitro, of the muscle interstitial fluid ~16-fold compared to perfusate. The magnitude of increase was similar for active exercise. The results demonstrate that a period of passive movement promotes endothelial cell proliferation and angiogenic factors and initiates capillarization in skeletal muscle.
Cyclic circumferential stretch and shear stress caused by pulsatile blood flow work in concert, yet are very different stimuli capable of independently mediating endothelial function by modulating eNOS expression, oxidative stress (via production of superoxide anion) and NO bioavailability. Porcine carotid arteries were perfused using an ex vivo arterial support system for 72 h. Groups we created by combining normal (5%) and reduced (1%) stretch with high shear (6 +/- 3 dynes/cm(2)) and oscillatory shear (0.3 +/- 3 dynes/cm(2)) stress while maintaining a pulse pressure of 80 +/- 10 mm Hg. Oscillatory flow and reduced stretch both proved detrimental to endothelial function, whereas oscillatory flow alone dominated total endogenous vascular wall superoxide anion production. Yet, when superoxide anion production was analyzed in just the endothelial region, we observed that it was modulated more significantly by reduced cyclic stretch than by oscillatory shear, emphasizing an important distinction between shear- and stretch-mediated effects to the vascular wall. Western blotting analysis of eNOS and nitrotyrosine proved that they too are more significantly negatively modulated by oscillatory flow than by reduced stretch. These findings point out how shear and stretch stimulate regions of the vascular wall differently, affecting NO bioavailability and contributing to vascular disease.
Changes in arterial shear stress induce functional and structural vasculature adaptations. Recent studies indicate that substantial retrograde flow and shear can occur through human conduit arteries. In animals, retrograde shear is associated with atherogenic effects. The aim of this study was to examine the impact of incremental levels of retrograde shear on endothelial function in vivo. On 3 separate days, we examined bilateral brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men (24+/-3 years) before and after a 30-minute intervention consisting of cuff inflation to 25, 50, or 75 mm Hg. Cuff inflations resulted in "dose"-dependent increases in retrograde shear rate, compared with the noncuffed arm, within subjects (P<0.001). Flow-mediated dilation in the cuffed arm did not change in response to the 25-mm Hg stimulus but decreased significantly after both the 50- and 75-mm Hg interventions (P<0.05). The decrease in flow-mediated dilation after the 75-mm Hg intervention was significantly larger than that observed after a 50-mm Hg intervention (P=0.03). In the noncuffed arm, no changes in shear rate or flow-mediated dilation were observed. These results demonstrate that an increase in retrograde shear rate induces a dose-dependent attenuation of endothelial function in humans. This finding contributes to our understanding regarding the possible detrimental effects of retrograde shear rate in vivo.
This study was conducted to examine whether stretch-related mechanical loading on skeletal muscle can suppress denervation-induced muscle atrophy, and if so, to depict the underlying molecular mechanism. Denervated rat soleus muscle was repetitively stretched (every 5 s for 15 min/day) for 2 weeks. Histochemical analysis showed that the cross-sectional area of denervated soleus muscle fibers with repetitive stretching was significantly larger than that of control denervated muscle (P<0.05). We then examined the involvement of the Akt/mammalian target of the rapamycin (mTOR) cascade in the suppressive effects of repetitive stretching on muscle atrophy. Repetitive stretching significantly increased the Akt, p70S6K, and 4E-BP1 phosphorylation in denervated soleus muscle compared to controls (P<0.05). Furthermore, repetitive stretching-induced suppression of muscle atrophy was fully inhibited by rapamycin, a potent inhibitor of mTOR. These results indicate that denervation-induced muscle atrophy is significantly suppressed by stretch-related mechanical loading of the muscle through upregulation of the Akt/mTOR signal pathway.
Older patients are thought to tolerate acute ischemia more poorly than younger patients. Since aging may depress both angiogenesis and arteriogenesis, we determined the effects of age on both angiogenesis and arteriogenesis in a model of severe acute limb ischemia.
Young adult (3-months-old) and aged (18-months-old) C57BL/6 mice underwent right common iliac artery and vein ligation and transection. Data were collected on days 0, 7, and 14. Perfusion was measured with a laser Doppler scan and compared to the contralateral limb. Functional deficits were evaluated with the Tarlov scale. Capillary density and endothelial progenitor cell (EPC) number were determined by direct counting lectin-positive/alpha-actin-negative cells and VEGFR2/CXCR4 dually-positive cells, respectively; angiography was performed to directly assess arteriogenesis.
Young adult and aged mice had a similar degree of decreased perfusion after iliac ligation (young, n = 15: 20.4 +/- 1.9%, vs aged, n = 20: 19.6 +/- 1.3%; P = .72, analysis of variance [ANOVA]); however, young mice recovered faster and to a greater degree than aged mice (day 7, 35 +/- 6% vs 17 +/- 4%, P = .046; day 14, 60 +/- 5% vs 27 +/- 7%, P = .0014). Aged mice had worse functional recovery by day 14 compared to young mice (2.3 +/- 0.3 vs 4.3 +/- 0.4; P = .0021). Aged mice had increased capillary density (day 7, 12.9 +/- 4.4 vs 2.8 +/- 0.3 capillaries/hpf; P = .02) and increased number of EPC incorporated into the ischemic muscle (day 7, 8.1 +/- 0.9 vs 2.5 +/- 1.9 cells; P = .007) compared to young mice, but diminished numbers of collateral vessels to the ischemic limb (1 vs 9; P = .01), as seen on angiography.
After severe hind limb ischemia, aged animals become ischemic to a similar degree as young animals, but aged animals have significantly impaired arteriogenesis and functional recovery compared to younger animals. These results suggest that strategies to stimulate arteriogenesis may complement those that increase angiogenesis, and may result in improved relief of ischemia.
Capillary orientation (anisotropy) was compared in hindlimb muscles of mammals of different size and/or different aerobic capacity (dog, goat, pony, and calf). All muscles were fixed by vascular perfusion at sarcomere lengths ranging from 1.5 to 2.7 micron. The ratios of capillary counts per fiber cross-sectional area on two sets of sections (0 and 90 degrees) to the muscle fiber axis were used to estimate capillary anisotropy and the coefficient c(K,0) relating 1) capillary counts on transverse sections (a commonly used parameter to assess muscle capillarity) and 2) capillary length per volume of fiber (i.e., capillary length density). Capillary orientation parallel to the muscle fiber axis decreased substantially with muscle fiber shortening. In muscles fixed at sarcomere lengths of 2.69 microns (dog vastus intermedius) and 1.52 microns (dog gastrocnemius), capillary tortuosity and branching added 7 and 64%, respectively, to capillary length density. The data obtained in this study are highly consistent with the previously demonstrated relationship between capillary anisotropy and sarcomere length in extended vs. contracted rat muscles, by use of the same method. Capillary anisotropy in mammalian locomotory muscles is curvilinearly related to sarcomere length. No systematic difference was found in capillary tortuosity with either body size, athletic ability, or aerobic capacity. Capillary tortuosity is a consequence of fiber shortening rather than an indicator of the O2 requirements of the tissue.
Previous studies on mice have revealed that the Griffonia simplicifolia I (GSI) lectin selectively binds to capillaries in a number of microvascular beds. These observations suggest that the lectin might be a suitable microvascular marker for physiological studies of skeletal muscle, particularly when fluorescent visualization of vessels is desired independently of their perfusion status. Since species and strain heterogeneity has been demonstrated for certain lectins associated with the microcirculatory vessels, lectin binding was studied in a number of muscles taken from the major species of mammals used for experimental purposes. Staining of cryostat sections confirmed the utility of GSI as a marker for capillaries from muscle of mice, rats, hamsters, rabbits, dogs, and monkeys. Differential staining of arterioles and veins was revealed by double labeling with GSI and antisera to Factor VIII-related antigen. Double labeling for GSI binding and alkaline phosphatase activity revealed that the GSI method detects many more capillaries and terminal arterioles than does the alkaline phosphatase method. GSI binding to unfixed whole mounts of thin skeletal muscles (hamster cheek pouch, mouse diaphragm, and rat cremaster) was studied to determine whether the GSI lectin would be a suitable marker for intravital studies. An extensive microvascular bed, including terminal arterioles, venules, and capillaries, was revealed which could be visualized in the complete absence of perfusion with fluorescent markers. These observations suggest that the GSI lectin may be extremely useful as a probe for the microcirculation of skeletal muscle in many types of physiological experiments.
A method for multiple simultaneous determinations of cardiocirculatory dynamics, regional blood flow, and total cardiac output distribution in the conscious rat preparation is described. The preparation allows for intravenous administration of agents and can be performed on animals either at rest or during treadmill exercise. Instrumentation procedures involve placement of fluid-filled catheters in the left ventricle, right atria, right jugular vein, and caudal artery. Left ventricular pressures are recorded via a modified 4F Millar transducer-tipped manometer containing a 10-cm extension of fluid-filled PE 50 placed into the left ventricle via the right carotid artery. Radionuclide-labeled microspheres (15 +/- 5 mu) are injected into the left ventricle through the fluid-filled PE 50 at selected times for determination of cardiac output and regional blood flows using the caudal artery catheter as the source of the reference blood sample. Details and selected validation data for procedures involving anesthesia, instrumentation, recovery from anesthesia, data gathering, and data analysis are presented. Emphasis is placed on the procedures required for use of the radioactive microsphere technique in this model with special attention given to quality control of the microsphere stock, counting procedures, and computer analysis of these data.
To assess the effect of age on cardiac volumes and function in the absence of overt or occult coronary disease, we performed serial gated blood pool scans at rest and during progressive upright bicycle exercise to exhaustion in 61 participants in the Baltimore Longitudinal Study of Aging. The subjects ranged in age from 25 to 79 years and were free of cardiac disease according to their histories and results of physical, resting and stress electrocardiographic, and stress thallium scintigraphic examinations. Absolute left ventricular volumes were obtained at each workload. There were no age-related changes in cardiac output, end-diastolic or end-systolic volumes, or ejection fraction at rest. During vigorous exercise (125 W), cardiac output was not related to age (cardiac output [1/min] = 16.02 + 0.03 [age]; r = .12, p = .46). However, there was an age-related increase in end-diastolic volume (end-diastolic volume [ml] = 86.30 + 1.48 [age]; r = .47, p = .003) and stroke volume (stroke volume [ml] = 85.52 + 0.80 [age]; r = .37, p = .02), and an age-related decrease in heart rate (heart rate [beats/min] = 184.66 - 0.70 [age]; r = -.50, p = .002). The dependence of the age-related increase in stroke volume on diastolic filling was emphasized by the fact that at this high workload end-systolic volume was higher (end-systolic volume [ml] = 3.09 + 0.65 [age]; r = .45, p = .003) and ejection fraction lower (ejection fraction = 88.48 - 0.18 [age]; r = -.33, p = .04) with increasing age. These findings indicate that although aging does not limit cardiac output per se in healthy community-dwelling subjects, the hemodynamic profile accompanying exercise is altered by age and can be explained by an age-related diminution in the cardiovascular response to beta-adrenergic stimulation.
A new model of stretch-induced growth is evaluated in four chicken wing muscles stretched to different extents by a spring-loaded tubular assembly. Muscles grew in length and cross section in proportion to the extent to which they were stretched. Longitudinal growth was essentially completed within 1 wk, while muscles grew in cross section through at least 5 wk of stretch. The muscles were neither denervated nor immobilized, and muscle activity as measured by EMG was not increased. Oxidative enzyme activities increased substantially with stretch in the patagialis (PAT), a twitch muscle, but were relatively unchanged in the slow-tonic anterior latissimus dorsi (ALD). Stretch altered mitochondrial enzyme proportions in the PAT, but had little effect in the ALD. Capillary density was unchanged with stretch in the PAT, but decreased in the ALD. Capillary density was unchanged with stretch in the PAT, but decreased in the ALD. Capillary-to-fiber ratio, however, increased in both muscles. We conclude that muscles grow and adapt enzymatically due to stretch, but that these responses are dissimilar in twitch and tonic muscles.
In vivo, endothelial cells (EC) are subjected to hemodynamic forces which may influence the production of nitric oxide. This study was designed to examine the effect of cyclic strain on the expression of endothelial nitric oxide synthase (eNOS) in cultured bovine aortic EC. EC were grown on flexible membranes which were subjected to deformation at 60 cycles/min with -5 or -20 kPa of vacuum. This results in an average strain of 6 and 10%, respectively, which is transmitted to the attached cells. Northern blot analysis of total cytosolic RNA demonstrated an increase in eNOS gene expression with both strain regimens but the increase with 10% average strain was greater than that at 6%. Nuclear runoff transcription assays confirmed the induction of eNOS transcripts. Western blot analysis showed an increase in eNOS level after 24 h of cyclic 10% average strain compared with controls or 6% average strain. Immunohistochemical staining of EC for eNOS was increased in the high strain periphery (7-24% strain) of membranes deformed with -20 kPa vacuum. These results demonstrate that cyclic strain upregulates the expression of eNOS transcripts and protein levels in bovine aortic EC thus emphasizing the importance of hemodynamic forces in the regulation of eNOS in vivo.
The present work was designed to elucidate the involvement of Ca(2+)-permeable stretch-activated (SA) channels in the orienting response of endothelial cells to uniaxial cyclic stretch. Endothelial cells from human umbilical vein were cultured on an elastic silicone membrane and subjected to uniaxial cyclic stretch (120% in length, 1 Hz). The cells started to change their morphology 15 min after the onset of stretch, and > 90% of the cells oriented perpendicularly to the stretch axis after 2 h. Associated with the orienting response, cell elongation proceeded with a slower rate. Both of the orientating and elongating responses were largely inhibited by the removal of external Ca2+ or by Gd3+, a potent blocker for the SA channel, but not by nifedipine. Intracellular Ca2+ concentration ([Ca2+]i) transiently increased in response to uniaxial stretch, and the basal [Ca2+]i gradually increased during cyclic stretch. This Ca2+ response was inhibited by the removal of extracellular Ca2+ or by the addition of Gd3+. These results suggest that stretch-dependent Ca2+ influx through SA channels is essential in the stretch-dependent cell orientation and elongation.
The hypothesis that changes in muscle activation and loading regulate the expression and activity of neuronal nitric oxide (NO) synthase (nNOS) was tested using in vitro and in vivo approaches. Removal of weight bearing from rat hindlimb muscles for 10 days resulted in a significant decrease in nNOS protein and mRNA concentration in soleus muscles, which returned to control concentrations after return to weight bearing. Similarly, the concentration of nNOS in cultured myotubes increased by application of cyclic loading for 2 days. NO release from excised soleus muscles was increased significantly by a single passive stretch of 20% or by submaximal activation at 2 Hz, although the increases were not additive when both stimuli were applied simultaneously. Increased NO release resulting from passive stretch or activation was dependent on the presence of extracellular calcium. Cyclic loading of cultured myotubes also resulted in a significant increase in NO release. Together, these findings show that activity of muscle influences NO production in the short term, by regulating NOS activity, and in the long term, by regulating nNOS expression.
Skeletal muscle blood flow is reduced as fibers are stretched longitudinally. Neither the underlying cause(s) of this decrement in blood flow nor the consequences in terms of capillary red blood cell (rbc) hemodynamics has been established clearly within the physiological range of muscle sarcomere length. Using intravital microscopy, this investigation determined arteriolar diameter and capillary rbc velocity (Vrbc), flux (Frbc), and hematocrit (Hct(t)) in the rat spinotrapezius muscle at shortened/resting (2.6 microm) and physiological extended (3.2 microm) sarcomere lengths under control (c) and local maximally vasodilated (v, phentolamine, 1 micromol/L; prazosin, 0.1 micromol/L; nitroprusside, 10 micromol/L) conditions. The hypothesis tested was that muscle stretch would reduce Vrbc and Frbc proportionally such that Hct(t) would remain unchanged and that these reductions in Vrbc and Frbc would be attenuated following maximal vasodilation. Vrbc and Frbc were increased significantly following maximal vasodilation at 2.6-microm (59 and 84%) and 3.2-microm (64 and 104%) sarcomere lengths, respectively. Irrespective of sarcomere length, Hct(t) was elevated significantly following vasodilation (c, 0.20 +/- 0.01; v, 0.27 +/- 0.01). At 3.2 microm compared with the 2.6-microm sarcomere length, Vrbc and Frbc were both reduced significantly under control and vasodilated conditions as expected. However, the percent reduction in either Vrbc (c, 27%, and v, 29%) or Frbc (c, 26%, and v, 33%) was not significantly different between the 2.6- and 3.2-microm sarcomere lengths. In addition, arteriolar diameter was not altered discernably as sarcomere length was increased from 2.7 microm (c, 29.0 +/- 4.5; v, 37.9 +/- 6.7 microm) to 3.2 microm (c, 29.4 +/- 4.5; v, 37.3 +/- 6.2 microm). These data suggest that increasing sarcomere length from resting to the upper extreme of the physiological range in the rat spinotrapezius muscle reduces Vrbc and Frbc (at constant hematocrit) by a mechanism that is independent of stretch-activated arteriolar vasoconstriction.
The relationship between skeletal muscle intracellular PO(2) (iPO(2)) and progressive muscular work has important implications for the understanding of O(2) transport and utilization. Presently there is debate as to whether iPO(2) falls progressively with increasing O(2) demand or reaches a plateau from moderate to maximal metabolic demand. Thus, using (1)H magnetic resonance spectroscopy of myoglobin (Mb), we studied cellular oxygenation during progressive single-leg knee extensor exercise from unweighted to 100% of maximal work rate in six active human subjects. In all subjects, the Mb peak at 73 ppm was not visible at rest, whereas the peak was small or indistinguishable from the noise in the majority of subjects during progressive exercise from unweighted to 50-60% of maximum work rate. In contrast, beyond this exercise intensity, a Mb peak of consistent magnitude was discernible in all subjects. When a Mb half saturation of 3.2 Torr was used, the calculated skeletal muscle PO(2) was variable before 60% of maximum work rate but in general was relatively high (>18 Torr, the measurable PO(2) with the poorest signal-to-noise ratio, in the majority of cases), whereas beyond this exercise intensity iPO(2) fell to a relatively uniform and invariant level of 3.8 +/- 0.5 Torr across all subjects. These results do not support the concept of a progressive linear fall in iPO(2) across increasing work rates. Instead, this study documents variable but relatively high iPO(2) from rest to moderate exercise and again confirms that from 50-60% of maximum work rate iPO(2) reaches a plateau that is then invariant with increasing work rate.
Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1alpha (HIF-1alpha). How mechanical stress affects the regulation of HIF-1alpha in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1alpha by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1alpha protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1alpha mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1alpha in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1alpha gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1alpha in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.
The anatomic size of the capillary-to-fiber (C/F) interface plays an important role in O(2) flux from blood to tissue by determining the surface area available for diffusion and is maintained in relative proportion to fiber mitochondrial volume across a wide range of muscle aerobic capacity. In the present study, we examined an estimate of the anatomic size of the C/F interface [the quotient of the individual C/F ratio and fiber perimeter, C/F perimeter exchange (CFPE) index] and fiber oxidative capacity in different skeletal muscles, or muscle regions, to test the hypothesis that capillarization would be maintained in relative excess of reduced fiber oxidative capacity in aged muscles. The right gastrocnemius, plantaris, and soleus muscles from young adult (8 mo old) and late middle-aged (28-30 mo old) Fischer 344 x Brown Norway F1 hybrid rats were excised for evaluation of flux through electron transport chain complexes I-III and/or morphometric estimation of capillarization. Muscle mass was lower in the gastrocnemius muscles of the older animals (2,076 +/- 32 vs. 1,825 +/- 47 mg in young adult vs. late middle-aged, respectively; mean +/- SE) but not the plantaris or soleus muscles. Fibers were smaller in the white region of gastrocnemius muscles but larger in the red region of gastrocnemius muscles of the older animals. There was no difference in the number of capillaries around a fiber, the individual C/F ratio, or the CFPE index between groups for any muscle/region, whereas flux through complexes I-III was reduced by 29-43% in late middle-aged animals. Thus the greater quotient of indexes of anatomic capillarity (individual C/F ratio or CFPE index) and fiber oxidative capacity in soleus and the white region of gastrocnemius muscles, but not in the red region of gastrocnemius muscles of the older animals, shows that anatomic capillarity is maintained in relative excess of oxidative capacity in some muscle regions in late middle-aged rats.
Hindlimb suspension unloading (HSU) is a ground-based model simulating the effects of microgravity unloading on the musculoskeletal system. In this model, gravity causes the hind foot of the rat to drop, opening the front of the ankle to 90-105 degrees plantar flexion at rest. As HSU proceeds, the normal weight-bearing angle of 30 degrees dorsiflexion is achieved progressively less, and the contraction range of soleus is abbreviated. Our laboratory reported that 12 days of HSU caused central corelike lesions (CCLs) of myofibril breakdown (Riley DA, Slocum GR, Bain JL, Sedlak FR, Sowa TE, and Mellender JW. J Appl Physiol. 69: 58-66, 1990). The present study investigated whether daily stretch of the calf muscles prevents CCL formation. The soleus muscles of HSU Sprague-Dawley male rats (approximately 287 g) were lengthened by unilateral ankle splinting at 30 degrees. Compared with the nonsplinted side, splinting for 10 or 20 min per day in awake rats significantly decreased CCLs in soleus by 88 and 91%, respectively (P < 0.01). Compared with control muscle wet weight, 20-min splinting reduced atrophy by 33%, whereas 10-min splinting ameliorated atrophy by 17% (P < 0.01). Bilateral soleus electromyograph recording revealed higher levels of contractile activity on the splinted side during splinting. To isolate the effects of stretch from isometric contractile activity, contractions were eliminated by whole animal anesthesia with isoflurane during 10-min daily splinting. The percentage of fibers with CCLs was reduced by 57%, and the average lesion size was 29% smaller in the stretched muscle (P < 0.05). Soleus muscle wet weight and fiber area were unaltered by stretch alone. Loaded contractions during splinting are necessary to prevent muscle fiber atrophy. Passive muscle stretch acts to maintain myofibril structural integrity.
Aging alters skeletal muscle vascular geometry and control such that the dynamics of muscular blood flow (Q) and O2 delivery (Q(O2)) may be impaired across the rest-exercise transition. If, at the onset of muscle contractions, Q dynamics are slowed disproportionately to those of muscle O2 uptake (V(O2), microvascular PO2 (PO2m) would be reduced and blood-tissue O2 transfer compromised. This investigation determined the effects of aging on PO2m (a direct reflection of the Q(O2)-to-V(O2) ratio), at rest and across the rest-contractions transition in the spinotrapezius of young (approximately 6 months, n = 9) and old (>24 months, n = 10) male Fisher 344/Brown Norway hybrid rats. Phosphorescence quenching techniques were used to quantify PO2m, and test the hypothesis that, across the rest-contractions (twitch, 1 Hz; 4-6 V, 240 s) transition, aging would transiently reduce the Q(O2)-to-V(O2) ratio causing a biphasic profile in which PO2m fell below steady-state contracting values. Old rats had a lower pre-contraction baseline PO2m than young (27.1+/-1.9 versus 33.8+/-1.6 mmHg, P<0.05, respectively). In addition, in old rats PO2m demonstrated a pronounced difference between the absolute nadir and end-contracting values (2.5+/-0.9 mmHg), which was absent in young rats. In conclusion, unlike their young counterparts, old rats exhibited a transiently reduced PO2m across the rest-contractions transition that may impair blood-tissue O2 exchange and elevate the O2 deficit, thereby contributing to premature fatigue.