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Leg vascular conductance (VC) at rest and during submaximal and maximal exercise with and without inhibition of nitric oxide formation ( l -NMMA) Modified from Rådegran & Saltin (1999).
Source publication
Contracting skeletal muscle can overcome sympathetic vasoconstrictor activity (functional sympatholysis), which allows for a blood supply that matches the metabolic demand. This ability is thought to be mediated by locally released substances that modulate the effect of noradrenaline (NA) on the α-receptor. Tyramine induces local NA release and can...
Context in source publication
Context 1
... sympathetic vaso- constriction. Firstly, exogenous NO stimulation of NO availability does not blunt sympathetic vasoconstriction (Rosenmeier et al. 2003). Secondly, inhibition of NO formation does not reduce exercise hyperaemia at the early onset or the steady-state levels even during maximal knee extensions where the SNA is markedly increase (Fig. 2) (Rådegran & Saltin, 1999;Savard et al. 1989). Although these observations point to a non-obligatory role of NO, it could act in synergy with other sub- stances such as prostacyclin ( Dinenno & Joyner, 2004) to mediate functional sympatholysis in a similar fashion as the combined role of these two substances in skeletal muscle ...
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Purpose
ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via purinergic P2 receptors. This study investigated the role of P2 receptors in exercise hyperemia in miniature swine.
Methods
We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and aft...
Citations
... Mortensen, 2012). This has been shown during single-leg kneeextensor exercise (KEE) using various techniques for leg blood flow (Q̇l eg ) assessment (Brønstad et al., 2012;Hartmann et al., 2022;Iepsen et al., 2017;Richardson et al., 2004). ...
Doppler ultrasound can be used to evaluate leg blood flow (Q̇ leg ), especially of interest when investigating peripheral vascular limitations in patients with chronic obstructive pulmonary disease (COPD). However, the within‐session repeatability, a subdomain of test‐retest reliability, of this method remains unknown. This study aimed to provide within‐session repeatability estimates of Doppler ultrasound‐based Q̇ leg at rest and during single‐leg knee‐extensor exercise (KEE) in patients with COPD, and to compare these estimates to matched healthy controls. In this case‐controlled study, 16 participants with COPD were matched based on sex and age with 16 healthy controls. All participants underwent measurement of Q̇ leg using Doppler ultrasound in a KEE setup at various intensities with the same measurement being performed again separated by 10 s. Smallest real difference (SRD) was lowest at rest in both groups and increased during exercise, reaching values ranging from 164 to 231 mL in COPD and 122–180 mL in the control group. The coefficient of variance (CV) was highest at rest and decreased during exercise to values ranging from 4.0% to 5.0% in COPD and 2.6%–3.2% in the control group. The CV was significantly lower in the control group during 0 watt and exercise at 20% of max watt, but apart from that, no reliability estimates were different between groups. To conclude, Doppler ultrasound showed nearly equal within‐session repeatability when evaluating Q̇ leg in COPD patients and healthy individuals with a CV not exceeding 5% during exercise for both groups.
... This finding is consistent with our previous results and another study, which showed that IPC remains relatively high in reactive hyperemia and persists for several minutes even during rest in both obese individuals (Jang et al., 2023) and those with lower limb occlusive arterial disease (Fudickar et al., 2014). High SmO 2 during exercise may result from either active vasodilation of the exercising muscles (Saltin and Mortensen, 2012) or suppressed vasoconstriction induced by sympathetic overactivation (Thomas and Segal, 2004), or a combination of both factors. In fact, we have previously confirmed that IPC inhibits sympathetic hyperactivation (Jang et al., 2023), and others also reported IPC-mediated improvement in NO bioavailability, which leads to vasodilation of exercising muscles (Lambert et al., 2016). ...
Introduction
A single bout of aerobic exercise is known to induce a temporary reduction in post-exercise blood pressure termed post-exercise hypotension (PEH). Meanwhile, an ischemic preconditioning (IPC), a series of short ischemia-reperfusion intervention, has also shown antihypertensive effects showing a potential nonpharmacologic intervention for hypertension. While the acute BP reduction effects of aerobic exercise and IPC are individually well-investigated, it remains unclear if combining both interventions has an additive effect on PEH.
Methods
A total of twelve pre- or hypertensive men (six prehypertension, six stage 1 hypertension) underwent either 30 min of aerobic exercise at 50% VO2peak (CON) or IPC before exercise, in a counterbalanced order. IPC involved inflating cuffs on both thighs to 200 mmHg for 5 min, alternating between right and left thighs for three cycles, totaling 30 min. Brachial BP was measured during exercise and 1-h post-exercise recovery whereas muscle oxygen saturation (SmO2) from the rectus femoris was monitored using NIRs during exercise and recovery. Heart rate variability (HRV) and baroreflex sensitivity (BRS) together with a head-up tilt test (at 0 and 50°) were measured at the pre-test, post-test, and 24-h post-test. After the completion of each experiment, 24-h ambulatory blood pressure (ABP) was monitored to assess post-exercise hypotension within a 24-h window.
Results
BP and heart rate responses during exercise and 1-h recovery did not differ between conditions while SmO2 was significantly elevated during exercise in IPC (p = 0.004). There was no difference in HRV and supine BRS. However, significantly reduced titled BRS after exercise was found in CON while IPC preserved BRS similar to pre-exercise value, extending to 24-h post period (p = 0.047). ABP monitoring revealed a significant reduction in systolic BP during sleep in IPC compared to CON (p = 0.046).
Conclusion
The present findings suggest that IPC with a single session of aerobic exercise results in a notable decrease in systolic ABP, particularly during sleep, compared to aerobic exercise alone. This supplementary antihypertensive effect was associated with a sustained BRS, persisting up to 24 h in contrast to the significant decrease observed in CON. Future studies are warranted to investigate long-term adaptations to IPC.
... The origin of peripheral vascular dysfunction in COPD is multifactorial. It includes altered redox balance with a reduced vascular bioavailability of nitric oxide (Ives et al., 2014) and complementary imbalance between other vasoactive substances within skeletal muscle that impairs functional sympatholysis (Haarmann et al., 2016;Ives et al., 2020;Saltin & Mortensen, 2012). Additionally, greater vascular stiffness potentially related to vascular inflammation (Eagan et al., 2010;Ives et al., 2014) in combination with reduced arterial elasticity (Kinlay et al., 2001) might also contribute to this peripheral vascular dysfunction. ...
Doppler ultrasound may be used to assess leg blood flow (Q̇leg), but the reliability of this method remains unexplored in patients with chronic obstructive pulmonary disease (COPD), where between‐subject variability may be larger than healthy due to peripheral vascular changes. This study aimed to investigate the reliability of Doppler ultrasound in quantifying Q̇leg during single‐leg knee‐extensor exercise (KEE) in COPD patients compared with those obtained from healthy matched controls. In this case–control study, 16 participants with COPD were matched based on sex and age with 16 healthy controls. All participants underwent measurement of Q̇leg using Doppler ultrasound in a KEE set‐up at various intensities on two separate visits. Confounding factors on Q̇leg were controlled for, and the ultrasound scans were consistently performed by the same sonographer. During exercise, smallest real difference (SRD) ranged from 367 mL to 583 mL in COPD and 438 mL to 667 mL in the control group. The coefficient of variation (CV) ranged from 7.9% to 14.3% in COPD and 9.4% to 10.4% in the control group. The intraclass correlation coefficient ranged from 0.75 to 0.92 in COPD and 0.67 to 0.84 in the control group. CV was lower in the control group during exercise at 0 W, but apart from that, reliability was not different between groups during exercise. Doppler ultrasound showed nearly equal reliability when evaluating Q̇leg in COPD patients and healthy individuals with a CV below 15% during exercise for both groups.
Highlights
What is the central question of this study?
What is the between‐day reliability of Doppler ultrasound when quantifying leg blood flow during single‐leg knee‐extensor exercise in COPD patients compared to healthy matched controls?
What is the main finding and its importance?
This study demonstrates a coefficient of variation ranging from 7.9 to 14.3% during single‐leg knee‐extensor exercise for between‐day reliability when applying Doppler ultrasound to assess leg blood flow in patients with COPD. Furthermore, it offers insights into the peripheral circulatory constraints in COPD, as evidenced by diminished leg blood flow. This study is the first of its kind to evaluate the reliability of Doppler ultrasound in the assessment of the peripheral circulation during exercise in COPD.
... In healthy adults, local vascular signals attenuate sympathetic vasoconstriction, a process referred to as 'functional sympatholysis' , to ensure adequate perfusion of metabolically active muscle. Without robust vasoconstriction in inactive tissues, blood pressure regulation and blood flow distribution are compromised and without appropriate functional sympatholysis, malperfusion of skeletal muscle reduces aerobic capacity (Saltin & Mortensen, 2012). Patients with HFpEF have documented increases in muscle sympathetic nervous system activity at rest. ...
... Muscle BF during exercise is regulated by the balance between local vasodilators, including NO and muscle metabolites, and vasoconstriction via sympathetic activity [14]. Aging and hypertension lower NO availability and impair the ability of contracting muscles to blunt sympathetic vasoconstriction during exercise (functional sympatholysis), reducing BF and oxygen delivery to skeletal muscles [15]. ...
... In the present study, there was a significant improvement in muscle oxygenation during exercise without an excessive BP response in postmenopausal women with hypertension after CIT supplementation compared to placebo. This could be explained by greater local artery vasodilation providing improved perfusion to contracting skeletal muscles [14], thereby increased oxygen delivery [25]. Taken together, 4 weeks of CIT supplementation was effective to improve muscle oxygenation and extraction during exercise in hypertensive postmenopausal women. ...
Endothelial dysfunction decreases exercise limb blood flow (BF) and muscle oxygenation. Acute L-Citrulline supplementation (CIT) improves muscle tissue oxygen saturation index (TSI) and deoxygenated hemoglobin (HHb) during exercise. Although CIT improves endothelial function (flow-mediated dilation [FMD]) in hypertensive women, the impact of CIT on exercise BF and muscle oxygenation (TSI) and extraction (HHb) are unknown. We examined the effects of CIT (10 g/day) and a placebo for 4 weeks on blood pressure (BP), arterial vasodilation (FMD, BF, and vascular conductance [VC]), and forearm muscle oxygenation (TSI and HHb) at rest and during exercise in 22 hypertensive postmenopausal women. Compared to the placebo, CIT significantly (p < 0.05) increased FMD (Δ−0.7 ± 0.6% vs. Δ1.6 ± 0.7%) and reduced aortic systolic BP (Δ3 ± 5 vs. Δ−4 ± 6 mmHg) at rest and improved exercise BF (Δ17 ± 12 vs. Δ48 ± 16 mL/min), VC (Δ−21 ± 9 vs. Δ41 ± 14 mL/mmHg/min), TSI (Δ−0.84 ± 0.58% vs. Δ1.61 ± 0.46%), and HHb (Δ1.03 ± 0.69 vs. Δ−2.76 ± 0.77 μM). Exercise BF and VC were positively correlated with improved FMD and TSI during exercise (all p < 0.05). CIT improved exercise artery vasodilation and muscle oxygenation via increased endothelial function in hypertensive postmenopausal women.
... The unique experimental design employed in the present study provided the opportunity to assess the impact of sympathoexcitation on microvascular reactivity without the in uence of metabolic vasodilation that accompanies voluntary exercise (47,48). This reductionist approach is particularly bene cial considering the complexity of neurovascular control during exercise, when sympathetic vasoconstriction to active skeletal muscle is diminished in direct relation to the exercise intensity, a phenomenon termed functional sympatholysis (49,50). Thus, the present investigation extends previous investigations examining the impact of augmented MSNA on skeletal muscle blood ow regulation during voluntary exercise (51)(52)(53)(54), offering new insight regarding the capacity of sympathetic nervous system activity to regulate muscle blood ow in the resting (inactive) and passively moved limbs. ...
Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.
... This process occurs in order to counteract increased sympathetic-mediated vasoconstriction, a phenomenon commonly called "functional sympatholysis" [18]. Functional sympatholysis is attenuated with age in females [19] and may be a chief mediator of reduced exercise hyperemia [20]. Thus, increased muscle sympathetic nerve activity (MSNA) during exercise after menopause [21] may augment vascular resistance and reduce superficial femoral artery blood flow (FA-BF) and oxygen consumption [22]. ...
... The final and most metabolically demanding exercise stage may have significantly augmented MSNA, and the leg muscle arterioles of the OB group were unable to compensate, leading to reduced exercise-mediated vasodilation. Vasodilator substances from contracting muscles and endothelium can attenuate sympathetic-mediated vasoconstriction [20]. Lower FA-BF and FA-VC in older males were associated with elevated sympathetic-mediated vasoconstriction and femoral vascular resistance [22]. ...
... The present study noted the OB group had significantly reduced whole-body LM percentage compared to the LN and OW. Previous findings have implicated poor muscular perfusion, as is apparent in individuals with OB, as a detriment to efficient functional sympatholysis [20]. Further, excessive adipose tissue storage is associated with increased MSNA and vascular resistance [47]. ...
Background
Obesity (OB) is highly prevalent in females after menopause, especially visceral adipose tissue (VAT) accumulation which contributes to endothelial dysfunction. The endothelium assists in regulating blood flow (BF) during exercise and is attenuated in females with OB. The purpose of this study was to examine upper and lower limb flow-mediated dilation (FMD) and BF regulation during graded low-intensity submaximal exercises in postmenopausal females with BMI in the lean (LN), overweight (OW) and OB categories.
Methods
Participants were grouped by body mass index (BMI) into LN (BMI 18.5–24.9 kg/m²; n = 11), OW (BMI 25.0–29.9 kg/m²; n = 15), and OB (BMI 30.0–39.9 kg/m²; n = 13). FMD of the brachial (BA-FMD) and superficial femoral arteries (FA-FMD) were assessed. Subsequently, BF and vascular conductance (VC) in the upper (BA-BF and BA-VC) and lower limbs (FA-BF and FA-VC) were measured during separate 3-stage incremental rhythmic handgrip and plantarflexion exercises.
Results
Significantly lower FA-FMD (P < 0.05) were seen in OB than LN and OW groups with no differences in BA-FMD. Increases in FA-BF and FA-VC were attenuated during the last stage of plantarflexion exercise at 30% of 1RM in OB (both P < 0.001) compared to LN and OW, while upper-body exercise vasodilation was unchanged. FA-BF and FA-VC during plantarflexion exercise were correlated to FA-FMD (FA-BF: r = 0.423, P = 0.007, FA-VC: r = 0.367, P = 0.021) and BMI (FA-BF: r = −0.386, P = 0.015, FA-VC: r = −0.456, P = 0.004).
Conclusion
Postmenopausal females with OB have reduced lower-limb endothelial and exercise vasodilator function during submaximal dynamic plantarflexion exercise compared to LN and OW. Our findings indicate that obesity may predict diminished leg endothelial function, BF and VC during exercise in postmenopausal females.
... Prior work has reported racial differences in exercise hyperemia without a difference in functional sympatholysis (52), highlighting that these outcomes can be dissociated. Functional sympatholysis has been identified as an underappreciated cause of poor contracting muscle perfusion (53) and may result in functional changes in exercise capacity (12). It has been shown that a high-fat diet can decrease aerobic exercise capacity (54). ...
A single high-fat Western meal transiently reduces endothelium-dependent vasodilation at rest but the interaction with sympathetic vasoconstrictor activity during exercise remains unknown. Herein, we tested the hypothesis that a single high-fat Western meal would impair the ability of contracting skeletal muscle to offset vascular responsiveness to sympathetic activation during exercise, termed functional sympatholysis. In 18 (10F/8M) healthy young adults, forearm blood flow (Doppler ultrasound) and beat-to-beat arterial pressure (photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) applied at rest and simultaneously during low- (15% maximum contraction) and moderate-intensity (30% maximum contraction) rhythmic handgrip. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes in forearm vascular conductance (FVC) between handgrip and rest. Experiments were performed preprandial and 1h, 2h, and 3h after a high- or low-fat meal. In the preprandial state, LBNP decreased resting FVC (∆-54±10%), and these responses were attenuated during low- (∆-17±7%) and moderate-intensity handgrip (∆-8±6%). Following a high-fat meal, LBNP induced attenuated decreases in resting FVC (3h postprandial: ∆-47±10%, P=0.002 vs. preprandial), and blunted attenuation of FVC during low- (3h postprandial: ∆-23±8%, P=0.001 vs. preprandial) and moderate-intensity handgrip (3h postprandial: ∆-16±6%, P<0.001 vs. preprandial). The high-fat meal attenuated the magnitude of sympatholysis during low- (preprandial: 38±7% vs. 3h postprandial: 23±8%, P<0.001) and moderate-intensity handgrip (preprandial: 46±11% vs. 3h postprandial: 31±10%, P<0.001). The low-fat meal had no impact on these responses. In conclusion, a single high-fat Western meal modulates sympathetic vasoconstriction at rest and during low- and moderate-intensity handgrip exercise in young healthy adults.
... Specifically, exercise-induced increases in sympathetic vasoconstrictor discharge promotes venous return to the heart which supports increases in left ventricular (LV) cardiac output ( _ Q c ), and vasoconstriction in non-active tissues serves to redistribute blood flow toward active skeletal muscle to meet the metabolic demands of exercise (1). Conversely, locally released metabolic by-products within active skeletal muscle offset sympathetically-mediated vasoconstriction (i.e., functional sympatholysis) to ensure blood supply matches the metabolic requirements of active muscle (2,3). This phenomenon is particularly important in the resistance arterioles of the muscle microcirculation (4). ...
... The concept of functional sympatholysis is the ability of active skeletal muscle to override sympathetic vasoconstrictor drive, ensuring adequate oxygen delivery to the muscle (2,3). While this physiological response is well-established in healthy humans, it is attenuated in diseases like elevated sympathetic activity (3). ...
Excessive sympathetic activity during exercise causes heightened peripheral vasoconstriction, which can reduce oxygen delivery to active muscles, resulting in exercise intolerance. Although both patients suffering from heart failure with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) exhibit reduced exercise capacity, accumulating evidence suggests that the underlying pathophysiology may be different between these two conditions. Unlike HFrEF, which is characterized by cardiac dysfunction with lower peak oxygen uptake, exercise intolerance in HFpEF appears to be predominantly attributed to peripheral limitations involving inadequate vasoconstriction rather than cardiac limitations. However, the relationship between systemic hemodynamics and the sympathetic neural response during exercise in HFpEF is less clear. This mini review summarizes the current knowledge on the sympathetic (i.e., muscle sympathetic nerve activity, plasma norepinephrine concentration) and hemodynamic (i.e., blood pressure, limb blood flow) responses to dynamic and static exercise in HFpEF compared to HFrEF, as well as non-HF controls. We also discuss the potential of a relationship between sympathetic over-activation and vasoconstriction leading to exercise intolerance in HFpEF. The limited body of literature indicates that higher peripheral vascular resistance, perhaps secondary to excessive sympathetically mediated vasoconstrictor discharge compared to non-HF and HFrEF, drives exercise in HFpEF. Excessive vasoconstriction also may primarily account for over elevations in blood pressure and concomitant limitations in skeletal muscle blood flow during dynamic exercise, resulting in exercise intolerance. Conversely, during static exercise, HFpEF exhibit relatively normal sympathetic neural reactivity compared to non-HF, suggesting that other mechanisms beyond sympathetic vasoconstriction dictate exercise intolerance in HFpEF.
... The parallel increase in norepinephrine and epinephrine observed in the study by Shim et al. [37] supports the view that both RAAS and sympathoadrenal system mutually interact in determining BP changes during physical exercise. The increased activity of both systems leading to peripheral arterial vasoconstriction may contribute to EBPR during exercise [38]. In this regard, studies conducted in hypertensive patients, in individuals with high-normal BP as well as in elderly men have suggested that hyper-activation of muscle chemoreceptors may attenuate functional sympatholysis, enhancing the vasoconstriction, which, in combination with increased cardiac output, is responsible of EBPR [39,40]. ...
The hypertensive response to exercise testing, defined as exaggerated blood pressure response (EBPR), has been documented to be independently associated with unhealthy conditions, carrying an increased risk of future hypertension, cardiovascular (CV) morbidity and mortality. In treated hypertensives, EBPR is a marker of uncontrolled hypertension, a condition previously undetected by office blood pressure (BP) measurements at rest; EBPR may also detect masked hypertension, a phenotype characterized by normal BP values in the medical environment but elevated home or ambulatory BP monitoring (ABPM). The aim of the present review is to provide a comprehensive and up-dated information on the clinical importance of EBPR targeting the following issues: (I) definition and prevalence; (II) underlying mechanisms; (III) clinical correlates and association with subclinical organ damage; (IV) predictive value; (V) clinical decision making.
