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ABSTRACT: Oscillatory and retrograde shear rate (SR) impairs endothelial function, potentially through shear-induced oxidative stress. We tested the hypothesis that acute vitamin C supplementation would prevent the attenuation of brachial artery flow-mediated dilation (FMD) after a period of augmented oscillatory and retrograde SR. Twelve healthy men (aged 26 ± 3 years) participated in two 30-min study visits in which one arm was subjected to increased oscillatory and retrograde SR, using 60 mm Hg of forearm cuff compression, and the contralateral arm served as the control. Subjects ingested capsules containing either placebo (sucrose) or vitamin C at 90 and 120 min (1000 mg total vitamin C) prior to cuff compression periods in a randomized placebo-controlled double-blind crossover study. Oscillatory and retrograde SR in the cuffed arms increased during the compression periods in the placebo and vitamin C study visits (p < 0.01 for both), with no difference between studies (p > 0.05). Antegrade SR remained unchanged throughout the compression periods (p > 0.05), and mean SR was lower in the cuffed arm than in the control arm for both study visits (p < 0.05). FMD decreased after cuff compression in the placebo cuffed arm (precompression vs. postcompression, 5.2% ± 1.4% vs. 3.5% ± 1.4%; p < 0.05), but remained unchanged after vitamin C therapy in the cuffed arm (precompression vs. postcompression, 5.3% ± 2.4% vs. 5.7% ± 2.6%; p > 0.05). No FMD changes were observed in the control arm for either study visit (p > 0.05). These data demonstrate that acute vitamin C supplementation prevents the attenuation of FMD due to altered SR patterns, suggesting that oxidative stress contributes to the oscillatory and retrograde SR-induced impairment of FMD.
Applied Physiology Nutrition and Metabolism 03/2013; 38(3):268-74. · 2.13 Impact Factor
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ABSTRACT: BACKGROUND: Acute doses of elevated retrograde shear rate (SR) appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1) increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD) in a dose-dependent manner, and (2) antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response. METHODS: Twelve men participated in four randomized exercise sessions (90 W for 20 minutes) on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg) (contralateral arm served as the control) and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session. RESULTS: Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P < 0.05) and without differences between cuff pressures (20 mmHg: 5.7 [PLUS-MINUS SIGN] 2.2 %; 40 mmHg: 4.7 [PLUS-MINUS SIGN] 1.3 %; 60 mmHg: 5.4 [PLUS-MINUS SIGN] 2.4 %) (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P < 0.05) but were not different (control: 7.1 [PLUS-MINUS SIGN] 3.5 % vs. cuffed: 6.6 [PLUS-MINUS SIGN] 3.3 %) (P > 0.05). CONCLUSIONS: These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose--response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and retrograde shear during exercise on FMD.
Cardiovascular Ultrasound 08/2012; 10(1):34. · 1.26 Impact Factor
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ABSTRACT: The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P < 0.01). BF and SR significantly diminished by 45 min of HF treatment only (P < 0.01). Both treatments reduced BF and SR and elevated oscillatory shear index compared with baseline (P < 0.01) during cuff inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.
Journal of Applied Physiology 03/2012; 112(12):2099-109. · 3.75 Impact Factor
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ABSTRACT: Despite the escalating prevalence in the aging population, few therapeutic options exist to treat patients with peripheral arterial disease. Application of intermittent pneumatic leg compressions (IPC) is regarded as a promising noninvasive approach to treat this condition, but the clinical efficacy, as well the mechanistic basis of action of this therapy, remain poorly defined. We tested the hypothesis that 2 wk of daily application of IPC enhances exercise tolerance by improving blood flow and promoting angiogenesis in skeletal muscle in a model of peripheral arterial insufficiency. Male Sprague-Dawley rats were subjected to bilateral ligation of the femoral artery and randomly allocated to treatment or sham groups. Animals were anesthetized daily and exposed to 1-h sessions of bilateral IPC or sham treatment for 14-16 consecutive days. A third group of nonligated rats was also studied. Marked increases in treadmill exercise tolerance (∼33%, P < 0.05) and improved muscle performance in situ (∼10%, P < 0.05) were observed in IPC-treated animals. Compared with sham-treated controls, blood flow measured with isotope-labeled microspheres during in situ contractions tended to be higher in IPC-treated animals in muscles composed of predominantly fast-twitch white fibers, such as the plantaris (∼93%, P = 0.02). Capillary contacts per fiber and citrate synthase activity were not significantly altered by IPC treatment. Collectively, these data indicate that IPC improves exercise tolerance in a model of peripheral arterial insufficiency in part by enhancing blood flow to collateral-dependent tissues.
Journal of Applied Physiology 02/2012; 112(9):1556-63. · 3.75 Impact Factor
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ABSTRACT: Intermittent pneumatic leg compressions (IPC) have proven to be an effective noninvasive approach for treatment of patients with claudication, but the mechanisms underlying the clinical benefits remain elusive. In the present study, a rodent model of claudication produced by bilateral ligation of the femoral artery was used to investigate the acute impact of a single session of IPC (150 min) on hemodynamics, skeletal muscle (tibialis anterior), and isolated collateral artery (perforating artery) expression of a subset of genes associated with inflammation and vascular remodeling. In addition, the effect of compression frequency (15 vs. 3 compressions/min) on the expression of these factors was studied. In ligated animals, IPC evoked an increase of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant 1 (CXCL1) mRNA (P < 0.01) and immunostaining (P < 0.05), as well as a minor increase in VEGF immunostaining in the muscle endomysium 150 min postintervention. Further, collateral arteries from these animals showed an increased expression of MCP-1 (approximately twofold, P = 0.02). These effects were most evident in the group exposed to the high-frequency protocol (15 compressions/min). In contrast, IPC in sham-operated control animals evoked a modest initial upregulation of VEGF (P = 0.01), MCP-1 (P = 0.02), and CXCL1 (P = 0.03) mRNA in the muscle without concomitant changes in protein levels. No changes in gene expression were observed in arteries isolated from sham animals. In conclusion, IPC acutely up-regulates the expression of important factors involved in vascular remodeling in the compressed muscle and collateral arteries in a model of hindlimb ischemia. These effects appear to be dependent on the compression frequency, such that a high compression frequency (15 compressions/min) evokes more consistent and robust effects compared with the frequency commonly employed clinically to treat patients with claudication (3 compressions/min).
AJP Regulatory Integrative and Comparative Physiology 09/2011; 301(6):R1658-68. · 3.34 Impact Factor
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ABSTRACT: Spinal cord injury leads to increased risk for cardiovascular disease and results in greater risk of death. Subclinical markers of atherosclerosis have been reported in carotid arteries of spinal cord-injured individuals (SCI), but the development of lower extremity peripheral arterial disease (PAD) has not been investigated in this population. The purpose of this study was to determine the effect of spinal cord injury on ankle-brachial index (ABI) and intima-media thickness (IMT) of upper-body and lower-extremity arteries. We hypothesized that the aforementioned measures of lower-extremity PAD would be worsened in SCI compared with controls and that regular participation in endurance exercise would improve these in both groups. To test these hypotheses, ABI and IMT were determined in 105 SCI and compared with 156 able-bodied controls with groups further subdivided into physically active and sedentary. ABIs were significantly lower in SCI versus controls (0.96 ± 0.12 vs. 1.06 ± 0.07, P < 0.001), indicating a greater burden of lower-extremity PAD. Upper-body IMTs were similar for brachial and carotid arteries in controls versus SCI. Lower extremity IMTs revealed similar thicknesses for both superficial femoral and popliteal arteries, but when normalized for artery diameter, individuals with SCI had greater IMT than controls in the superficial femoral (0.094 ± 0.03 vs. 0.073 ± 0.02 mm/mm lumen diameter, P < 0.01) and popliteal (0.117 ± 0.04 vs. 0.091 ± 0.02 mm/mm lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared with controls indicate that subclinical measures of lower-extremity PAD are worsened in individuals with SCI. These findings should prompt physicians to consider using the ABI as a screening method to detect lower-extremity PAD in SCI.
AJP Heart and Circulatory Physiology 07/2011; 301(3):H766-72. · 3.71 Impact Factor
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ABSTRACT: The mechanisms underlying the unequal distribution of atherosclerotic disease in the peripheral arteries are currently unclear. Gene expression differences in healthy arteries may influence the heterogeneous distribution of atherosclerosis. Therefore, this investigation compares gene expression in healthy atheroprotected brachial and atherosusceptible femoral arteries of young and disease free Rapacz familial hypercholesterolemic (FHC) swine. We hypothesized that transcripts related to atherosusceptibility would be differentially expressed between these arteries prior to the onset of disease. Femoral and brachial arteries were harvested from four 13-day-old Rapacz FHC swine. No atherosclerotic disease was detected using Sudan IV, Verhoeff-van Gieson, and hematoxylin-eosin staining. Gene expression was quantified using Affymetrix GeneChip Porcine Genome Arrays. An average of 15,552 probe sets had detectable transcripts, while 430 probe sets showed a significant differential expression between arteries (false discovery rate < 0.05). The human orthologs of 63 probe sets with differential expression and a 1.5-fold or greater transcript abundance between arteries are associated with Wnt/β-catenin, lysophospholipid, and Ca-signaling, as well as apoptosis. This is the first investigation reporting that differences in relative abundance of gene expression exist between brachial and femoral arteries in young Rapacz FHC swine prior to the development of atherosclerotic lesions.
Physiological Genomics 04/2011; 43(12):781-8. · 2.73 Impact Factor
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Journal of Applied Physiology 03/2011; 110(5):1156-7. · 3.75 Impact Factor
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ABSTRACT: Physical activity, exercise training, and fitness are associated with decreased cardiovascular risk. In the context that a risk factor "gap" exists in the explanation for the beneficial effects of exercise on cardiovascular disease, it has recently been proposed that exercise generates hemodynamic stimuli which exert direct effects on the vasculature that are antiatherogenic. In this review we briefly introduce some of the in vitro and in vivo evidence relating exercise hemodynamic modulation and vascular adaptation. In vitro data clearly demonstrate the importance of shear stress as a potential mechanism underlying vascular adaptations associated with exercise. Supporting this is in vivo human data demonstrating that exercise-mediated shear stress induces localized impacts on arterial function and diameter. Emerging evidence suggests that exercise-related changes in hemodynamic stimuli other than shear stress may also be associated with arterial remodeling. Taken together, in vitro and in vivo data strongly imply that hemodynamic influences combine to orchestrate a response to exercise and training that regulates wall stress and peripheral vascular resistance and contributes to the antiatherogenic impacts of physical activity, fitness, and training.
Journal of Applied Physiology 03/2011; 111(1):311-20. · 3.75 Impact Factor
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ABSTRACT: Functional and structural heterogeneity exists among skeletal muscle vascular beds related, in part, to muscle fiber type composition. This study was designed to delineate whether the vulnerability to vascular dysfunction in insulin resistance is uniformly distributed among skeletal muscle vasculatures and whether physical activity modifies this vulnerability. Obese, hyperphagic Otsuka Long-Evans Tokushima fatty rats (20 wk old) were sedentary (OSED) or physically active (OPA; access to running wheels) and compared with age-matched sedentary Long-Evans Tokushima Otsuka (LSED) rats. Vascular responses were determined in isolated, pressurized feed arteries from fast-twitch gastrocnemius (GFAs) and slow-twitch soleus (SFAs) muscles. OSED animals were obese, insulin resistant, and hypertriglyceridemic, traits absent in LSED and OPA rats. GFAs from OSED animals exhibited depressed dilation to ACh, but not sodium nitroprusside, and enhanced vasoconstriction to endothelin-1 (ET-1), but not phenylephrine, compared with those in LSED. Immunoblot analysis suggests reduced endothelial nitric oxide synthase phosphorylation at Ser1177 and endothelin subtype A receptor expression in OSED GFAs. Physical activity prevented reduced nitric oxide-dependent dilation to ACh, but not enhanced ET-1 vasoconstriction, in GFA from OPA animals. Conversely, vasoreactivity of SFAs to ACh and ET-1 were principally similar in all groups, whereas dilation to sodium nitroprusside was enhanced in OSED and OPA rats. These data demonstrate, for the first time, that SFAs from insulin-resistant rats exhibit reduced vulnerability to dysfunction versus GFAs and that physical activity largely prevents GFA dysfunction. We conclude that these results demonstrate that vascular dysfunction associated with insulin resistance is heterogeneously distributed across skeletal muscle vasculatures related, in part, to muscle fiber type and activity level.
AJP Heart and Circulatory Physiology 02/2011; 300(4):H1434-41. · 3.71 Impact Factor
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ABSTRACT: In humans, the measurement of brachial artery endothelial vasomotor function is used as a surrogate index of systemic endothelial health; however, the applicability of brachial artery findings to other vasculatures needs to be examined. The purpose of the present investigation was to test the following hypotheses: (1) brachial and femoral artery endothelium-dependent/independent relaxation is correlated; (2) endothelial expression of pro-/antiatherogenic proteins is correlated between brachial and femoral arteries; and (3) within vessel, there is a positive correlation between expression of antiatherogenic proteins and endothelium-dependent/independent relaxation, and an inverse correlation between expression of proatherogenic proteins and relaxation. In vitro endothelium-dependent (bradykinin [BK] and acetylcholine [Ach]) and -independent (sodium nitroprusside [SNP]) relaxation were evaluated in harvested brachial and femoral arteries of 96 Yucatan miniature swine. In a subset of pigs (n = 32), expression of 18 pro-/antiatherogenic proteins was measured from brachial and femoral artery endothelial cell scrapes using immunoblot analysis. Vascular sensitivity (half-maximal effective dose) to BK, Ach and SNP was highly correlated between brachial and femoral arteries (P < 0.01). A significant correlation was found between brachial and femoral arteries for content of six of the 18 measured proteins (P < 0.01). Furthermore, expression of two proteins (eNOS and COX-1) was correlated with vasorelaxation function in the brachial artery (P < 0.01). We provide the first evidence of a relationship between brachial and femoral artery endothelium-dependent relaxation. Our data also suggest that, in general terms, endothelial expression of several established pro-/antiatherogenic proteins is not robustly associated between brachial and femoral arteries, and does not link strongly to vasorelaxation function.
Experimental Biology and Medicine 11/2010; 235(11):1287-91. · 2.64 Impact Factor
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ABSTRACT: During dynamic exercise, the vasculature embedded within skeletal muscle intermittently collapses due to increased intramuscular pressure (IMP). The aim of this study was to ascertain whether oscillations in IMP during muscle contractions independently contribute to exercise training-induced increases in blood flow capacity (BFC). Based on IMP measurements during handgrip exercise, we attempted to mimic the action of repeated vascular compressions by using external inflatable cuffs. Thus, 24 healthy young male subjects underwent a 4-week program (5 days/week, 1 h/day) of application of external compressions of the non-dominant forearm, while the dominant limb served as an internal control. To evaluate the impact of compression pressures of different magnitudes, subjects were randomly assigned to one of three groups: 50, 100 and 150 mmHg of external compression. Prior to the intervention and after 2 and 4 weeks of treatment, we measured peak forearm blood flow (PBF) (Doppler ultrasound) and calculated peak vascular conductance (PVC) following 10 min of forearm ischemia. In the 50 and 100 mmHg groups, application of intermittent compressions did not alter PBF in either control or intervention forearms. In the 150 mmHg group, there was a trend (P = 0.04) for greater increases in PBF from baseline after 4 weeks in the intervention forearm compared to the control forearm (delta PBF: 4.2 ± 2.5 vs. -2.1 ± 2.0 (ml(100 ml)(-1) min(-1)), in the intervention and control forearms, respectively), but the changes in PVC were not significant (P = 0.1). These findings suggest that repeated oscillations in IMP contribute minimally to exercise-induced increase in forearm BFC in healthy young humans.
Arbeitsphysiologie 10/2010; 111(3):509-19. · 2.15 Impact Factor
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ABSTRACT: Although the beneficial effects of exercise training on conduit artery endothelial function are well-established in animals and humans with compromised basal function, whether exercise exerts favorable effects on a healthy endothelium is inconclusive. We sought to determine whether long-term exercise training enhances endothelial function in peripheral conduit arteries of healthy pigs. Using a retrospective analysis of data collected in our laboratory (n = 127), we compared in vitro brachial and femoral artery endothelium-dependent and -independent relaxation between a group of pigs that exercise-trained for 16-20 wk and a group that remained sedentary. No differences in vasomotor function were found between the 2 groups (P > 0.05). Additionally, in a subset of pigs (n = 16), expression levels of 18 proteins that are typically associated with the atherosclerotic process were measured by immunoblot analysis of endothelial cell scrapes obtained from the brachial and femoral arteries. We found no differences (P > 0.05) in endothelial gene expression between these exercise-trained and sedentary healthy pigs. These results indicate that pigs exhibiting the classic training-induced adaptations do not demonstrate enhanced endothelium-dependent dilation nor reveal a more atheroprotected endothelial cell phenotype in their brachial and femoral arteries than their sedentary but otherwise healthy counterparts.
AJP Heart and Circulatory Physiology 08/2010; 299(2):H379-85. · 3.71 Impact Factor
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ABSTRACT: Escalating evidence indicates that disturbed flow patterns, characterized by the presence of retrograde and oscillatory shear stress, induce a proatherogenic endothelial cell phenotype; however, the mechanisms underlying oscillatory shear profiles in peripheral conduit arteries are not fully understood. We tested the hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are accompanied by increases in conduit artery retrograde and oscillatory shear. Fourteen healthy men (25 +/- 1 yr) performed three sympathoexcitatory maneuvers: graded lower body negative pressure (LBNP) from 0 to -40 Torr, cold pressor test (CPT), and 35% maximal voluntary contraction handgrip followed by postexercise ischemia (PEI). MSNA (microneurography; peroneal nerve), arterial blood pressure (finger photoplethysmography), and brachial artery velocity and diameter (duplex Doppler ultrasound) in the contralateral arm were recorded continuously. All maneuvers elicited significant increases in MSNA total activity from baseline (P < 0.05). Retrograde shear (-3.96 +/- 1.2 baseline vs. -8.15 +/- 1.8 s(-1), -40 LBNP, P < 0.05) and oscillatory shear index (0.09 +/- 0.02 baseline vs. 0.20 +/- 0.02 arbitrary units, -40 LBNP, P < 0.05) were progressively augmented during graded LBNP. In contrast, during CPT and PEI, in which MSNA and blood pressure were concomitantly increased (P < 0.05), minimal or no changes in retrograde and oscillatory shear were noted. These data suggest that acute elevations in MSNA are associated with an increase in conduit artery retrograde and oscillatory shear, an effect that may be influenced by concurrent increases in arterial blood pressure. Future studies should examine the complex interaction between MSNA, arterial blood pressure, and other potential modulatory factors of shear rate patterns.
AJP Heart and Circulatory Physiology 04/2010; 298(4):H1128-35. · 3.71 Impact Factor
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ABSTRACT: Application of intermittent pneumatic compressions (IPC) is an extensively used therapeutic strategy in vascular medicine, but the mechanisms by which this method works are unclear. We tested the hypothesis that acute application (150 min) of cyclic leg compressions in a rat model signals upregulation of angiogenic factors in skeletal muscle. To explore the impact of different pressures and frequency of compressions, we divided rats into four groups as follows: 120 mmHg (2 s inflation/2 s deflation), 200 mmHg (2 s/2 s), 120 mmHg (4 s/16 s), and control (no intervention). Blood flow and leg oxygenation (study 1) and the mRNA expression of angiogenic mediators in the rat tibialis anterior muscle (study 2) were assessed after a single session of IPC. In all three groups exposed to the intervention, a modest hyperemia (approximately 37% above baseline) between compressions and a slight, nonsignificant increase in leg oxygen consumption (approximately 30%) were observed during IPC. Compared with values in the control group, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) mRNA increased significantly (P < 0.05) only in rats exposed to the higher frequency of compressions (2 s on/2 s off). Endothelial nitric oxide synthase, matrix metalloproteinase-2, and hypoxia-inducible factor-1alpha mRNA did not change significantly following the intervention. These findings show that IPC application augments the mRNA content of key angiogenic factors in skeletal muscle. Importantly, the magnitude of changes in mRNA expression appeared to be modulated by the frequency of compressions such that a higher frequency (15 cycles/min) evoked more robust changes in VEGF and MCP-1 compared with a lower frequency (3 cycles/min).
AJP Heart and Circulatory Physiology 03/2010; 298(6):H1991-2000. · 3.71 Impact Factor
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ABSTRACT: Although normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress (FMD:shear stress ratio) has been proposed to improve this measure of endothelial function, the clinical utility of FMD normalization has not yet been demonstrated. We tested (1) whether following conventional 5-min forearm occlusion, the FMD:shear stress ratio would discriminate a population with moderate cardiovascular risk (MR) from a low-risk (LR) population, and (2) whether the dose-response profile relating shear stress to FMD would be different between the 2 populations.
Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 MR and 20 LR subjects by manipulating forearm cuff occlusion duration. Brachial artery diameters and velocities were measured via high-resolution ultrasound. To quantify the hyperemic stimulus, shear stress area under the curve was individually calculated for the duration of time-to-peak dilation.
Following 5-min of forearm occlusion, FMD:shear stress ratio (p = 0.041), but not FMD (p = 0.286), discriminated MR from LR. The slope of the shear stress-FMD regression line was lower in MR compared to the LR (p < 0.001).
The FMD:shear stress ratio distinguished reduced endothelial function in a population with MR. The dose-response profile of the shear stress-FMD relationship appears to differ between populations of distinct cardiovascular risk.
Journal of Vascular Research 07/2009; 46(6):592-600. · 2.65 Impact Factor
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ABSTRACT: Unlike quadrupeds, humans exhibit a larger hydrostatic pressure in the lower limbs compared with the upper limbs during a major part of the day. It is plausible that repeated episodes of elevated pressure in the legs may negatively impact the endothelium, hence contributing to the greater predisposition of atherosclerosis in the legs. We tested the hypothesis that an acute exposure to increased hydrostatic pressure would induce conduit artery endothelial dysfunction. In protocol 1, to mimic the hemodynamic environment of the leg, we subjected the brachial artery to a hydrostatic pressure gradient ( approximately 15 mmHg) by vertically hanging the arm for 3 h. Brachial artery flow-mediated dilation (FMD) was assessed in both arms before and following the intervention. In protocol 2, we directly evaluated popliteal artery FMD before and after a 3-h upright sitting (pressure gradient approximately 48 mmHg) and control (supine position) intervention. Our arm-hanging model effectively resembled the hemodynamic milieu (high pressure and low shear rate) present in the lower limbs during the seated position. Endothelium-dependent vasodilation at the brachial artery was attenuated following arm hanging (P < 0.05); however, contrary to our hypothesis, upright sitting did not have an impact on popliteal artery endothelial function (P > 0.05). These data suggest an intriguing vascular-specific response to increased hydrostatic pressure and reduced shear rate. Further efforts are needed to determine if this apparent protection of the leg vasculature against an acute hydrostatic challenge is attributable to posture-induced chronic adaptations.
AJP Heart and Circulatory Physiology 07/2009; 297(3):H1103-8. · 3.71 Impact Factor
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ABSTRACT: Shear stress is an important stimulus to arterial adaptation in response to exercise and training in humans. We recently observed significant reverse arterial flow and shear during exercise and different antegrade/retrograde patterns of shear and flow in response to different types of exercise. The purpose of this study was to simultaneously examine flow-mediated dilation, a largely NO-mediated vasodilator response, in both brachial arteries of healthy young men before and after 30-minute interventions consisting of bilateral forearm heating, recumbent leg cycling, and bilateral handgrip exercise. During each intervention, a cuff inflated to 60 mm Hg was placed on 1 arm to unilaterally manipulate the shear rate stimulus. In the noncuffed arm, antegrade flow and shear increased similarly in response to each intervention (ANOVA; P<0.001, no interaction between interventions; P=0.71). Baseline flow-mediated dilation (4.6%, 6.9%, and 6.7%) increased similarly in response to heating, handgrip, and cycling (8.1%, 10.4%, and 8.9%, ANOVA; P<0.001, no interaction; P=0.89). In contrast, cuffed arm antegrade shear rate was lower than in the noncuffed arm for all of the conditions (P<0.05), and the increase in flow-mediated dilation was abolished in this arm (4.7%, 6.7%, and 6.1%; 2-way ANOVA: all conditions interacted P<0.05). These results suggest that differences in the magnitude of antegrade shear rate transduce differences in endothelial vasodilator function in humans, a finding that may have relevance for the impact of different exercise interventions on vascular adaptation in humans.
Hypertension 06/2009; 54(2):278-85. · 6.21 Impact Factor
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Cardiovascular Ultrasound 10/2008; · 1.26 Impact Factor
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ABSTRACT: Current evidence indicates that the ability of physical activity to sustain a normal phenotype of arterial endothelial cells (ECs) plays a central role in the beneficial effects of exercise (Ex) on atherosclerotic disease. Here we evaluate the strength of evidence that shear stress (SS) and/or circumferential wall stress (stretch) are the primary signals, produced by bouts of Ex, that signal altered gene expression in arterial ECs, thereby resulting in a less atherogenic EC phenotype. Current literature indicates that SS is a signal for expression of antiatherogenic genes in cultured ECs, in ECs of isolated arteries, and in ECs of arteries in intact animals. Furthermore, SS levels in the arteries of humans during Ex are in the range that produces beneficial changes. In contrast, complex flow profiles within recirculation zones and/or oscillatory flow patterns can cause proatherogenic gene expression in ECs. In vivo evidence indicates that Ex decreases oscillatory flow/SS in some portions of the arterial tree but may increase oscillatory flow in other areas of the arterial tree. Circumferential wall stress can increase expression of some beneficial EC genes as well, but circumferential wall stress also increases production of reactive oxygen species and increases the expression of adhesion factors and other proatherogenic genes. Interactions of arterial pressure and fluid SS play an important role in arterial vascular health and likely contribute to how Ex bouts signal changes in EC gene expression. It is also clear that other local and circulating factors interact with these hemodynamic signals during Ex to produce the healthy arterial EC phenotype. We conclude that available evidence suggests that exercise signals formation of beneficial endothelial cell phenotype at least in part through changes in SS and wall stretch in the arteries.
Journal of Applied Physiology 04/2008; 104(3):588-600. · 3.75 Impact Factor
