scholarly journals Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress

2016 ◽  
Vol 310 (5) ◽  
pp. H648-H653 ◽  
Author(s):  
Robert M. Restaino ◽  
Lauren K. Walsh ◽  
Takuma Morishima ◽  
Jennifer R. Vranish ◽  
Luis A. Martinez-Lemus ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Internal Control ◽  
Popliteal Artery ◽  
Local Heating ◽  
Underlying Mechanism ◽  
Flow Mediated Dilation ◽  
Prolonged Sitting ◽  
Artery Flow

We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s−1; and 3-h sit, 23.6 ± 3.3 s−1; P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s−1; and 3-h sit, 63.9 ± 16.9 s−1; P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress.

scholarly journals Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction

2017 ◽  
Vol 131 (11) ◽  
pp. 1045-1053 ◽  
Author(s):  
Takuma Morishima ◽  
Robert M. Restaino ◽  
Lauren K. Walsh ◽  
Jill A. Kanaley ◽  
Jaume Padilla
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Popliteal Artery ◽  
Local Heating ◽  
Standing Position ◽  
Prolonged Sitting ◽  
Prior Exercise ◽  
Significant Impairment ◽  
Experimental Trials ◽  
Artery Flow

We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: (1) sitting without prior exercise; (2) sitting with prior exercise; and (3) standing without prior exercise. Following baseline popliteal artery flow-mediated dilation (FMD) measurements, subjects maintained a supine position for 45 min in the sitting and standing trials, without prior exercise, or performed 45 min of leg cycling before sitting (i.e. sitting with prior exercise trial). Thereafter, subjects were positioned into a seated or standing position, according to the trial, for 3 h. Popliteal artery FMD measures were then repeated. Three hours of sitting without prior exercise caused a significant impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%, P<0.05), which was prevented when sitting was preceded by a bout of cycling exercise (baseline: 3.8±0.5%, post-sitting: 3.6±0.7%, P>0.05). Three hours of standing did not significantly alter popliteal artery FMD (baseline: 4.1±0.4%, post-standing: 4.3±0.4%, P>0.05). In conclusion, prolonged sitting-induced leg endothelial dysfunction can be prevented by prior aerobic exercise. In addition, in the absence of exercise, standing represents an effective substitute to sitting for preserving leg conduit artery endothelial function.

scholarly journals Prolonged sitting-induced leg endothelial dysfunction is prevented by fidgeting

2016 ◽  
Vol 311 (1) ◽  
pp. H177-H182 ◽  
Author(s):  
Takuma Morishima ◽  
Robert M. Restaino ◽  
Lauren K. Walsh ◽  
Jill A. Kanaley ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Shear Rate ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Popliteal Artery ◽  
Artery Blood Flow ◽  
Pronounced Increase ◽  
Prolonged Sitting ◽  
Leg Movement

Prolonged sitting impairs endothelial function in the leg vasculature, and this impairment is thought to be largely mediated by a sustained reduction in blood flow-induced shear stress. Indeed, preventing the marked reduction of shear stress during sitting with local heating abolishes the impairment in popliteal artery endothelial function. Herein, we tested the hypothesis that sitting-induced reductions in shear stress and ensuing endothelial dysfunction would be prevented by periodic leg movement, or “fidgeting.” In 11 young, healthy subjects, bilateral measurements of popliteal artery flow-mediated dilation (FMD) were performed before and after a 3-h sitting period during which one leg was subjected to intermittent fidgeting (1 min on/4 min off) while the contralateral leg remained still throughout and served as an internal control. Fidgeting produced a pronounced increase in popliteal artery blood flow and shear rate (prefidgeting, 33.7 ± 2.6 s−1 to immediately postfidgeting, 222.7 ± 28.3 s−1; mean ± SE; P < 0.001) that tapered off during the following 60 s. Fidgeting did not alter popliteal artery blood flow and shear rate of the contralateral leg, which was subjected to a reduction in blood flow and shear rate throughout the sitting period (presit, 71.7 ± 8.0 s−1 to 3-h sit, 20.2 ± 2.9 s−1; P < 0.001). Popliteal artery FMD was impaired after 3 h of sitting in the control leg (presit, 4.5 ± 0.3% to postsit: 1.6 ± 1.1%; P = 0.039) but improved in the fidgeting leg (presit, 3.7 ± 0.6% to postsit, 6.6 ± 1.2%; P = 0.014). Collectively, the present study provides evidence that prolonged sitting-induced leg endothelial dysfunction is preventable with small amounts of leg movement while sitting, likely through the intermittent increases in vascular shear stress.

Abstract 530: Impact of a Single Mixed Mediterranean-Type Meal Compared with a High-Saturated Fat Meal on Postprandial Endothelial Function and Metabolic Markers

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Sebastien Lacroix ◽  
Christine Des Rosiers ◽  
Mathieu Gayda ◽  
Anil Nigam
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Saturated Fat ◽  
Random Order ◽  
Flow Mediated Dilation ◽  
Omega 3 ◽  
Metabolic Markers ◽  
Endothelial Impairment ◽  
Artery Flow ◽  
Fat Meal

Background: Endothelial dysfunction is considered a precursor of atherosclerosis and is an independent predictor of cardiovascular events. A high-saturated fat meal (HFM) has been shown to induce postprandial endothelial dysfunction. However, no studies have evaluated the acute endothelial effect of a single mixed Mediterranean-type meal (MMM). Our objective was to evaluate postprandial endothelial and metabolic function in response to a MMM in comparison to an isocaloric HFM. Methods: In this ongoing crossover study, 26 of 28 healthy non-smoking males have completed the research protocol. In random order on two separate days during a 1-week interval, subjects were fed two isocaloric meals after an overnight fast. The MMM (885 kcal) consisted of fresh salmon, almonds and vegetables baked in olive oil providing 51% of total calories from fat (7.87g SFA and 2.29g of omega-3, 2:1 DHA:EPA). The HFM consisted of a McDonald’s sausage, egg and cheese McMuffin and three hashbrowns (858 kcal) providing 58% of total energy from fat (14.78g SFA and no omega-3). Endothelial function was evaluated by measuring brachial artery flow-mediated dilation (%FMD) at baseline and at two (T2) and four (T4) hours postprandial. Results: Mean postprandial %FMD tends to be less impaired following the MMM than the HFM (variation at T4 -0.15±3.6% vs -2.83±3.3% respectively, p<0.1). Postprandial variations of TG and TG/HDL at T4 were also less severe with the MMM than the HFM (p≤0.05) and did not correlate to %FMD variations. When subdividing the population on the basis of the median fasting TG levels (0.90 mmol/L), the HFM led to significant endothelial impairment in the subjects with higher-TG while it had no effect in the low-TG group. Conclusion: Our data suggest that a single MMM exerts less of a deleterious effect on postprandial endothelial function and metabolic markers than does a HFM. A single MMM could thus be less atherogenic than a HFM. Moreover, subjects with higher fasting TG levels (avg. 1.54±0.59 mmol/L, well bellow hypertriglyceridemia threshold) could be at higher risk of endothelial injury following a single HFM. Data on all 28 subjects will be available in April 2012.

Isometric handgrip training does not improve flow-mediated dilation in subjects with normal blood pressure

2007 ◽  
Vol 112 (7) ◽  
pp. 403-409 ◽  
Author(s):  
Cheri L. Mcgowan ◽  
Andrew S. Levy ◽  
Neil Mccartney ◽  
Maureen J. Macdonald
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Internal Control ◽  
Repeated Measures ◽  
Flow Mediated Dilation ◽  
Normal Blood Pressure ◽  
Isometric Handgrip ◽  
Repeated Measures Design ◽  
Artery Flow ◽  
Maximal Effort

Isometric HG (handgrip) training lowers resting arterial BP (blood pressure), yet the mechanisms are elusive. In the present study, we investigated improved systemic endothelial function as a mechanism of arterial BP modification following isometric HG training in normotensive individuals. This study employed a within-subject repeated measures design primarily to assess improvements in BA FMD (brachial artery flow-mediated dilation; an index of endothelium-dependent vasodilation), with the non-exercising limb acting as an internal control. Eleven subjects performed four 2-min unilateral isometric HG contractions at 30% of maximal effort, three times per week for 8 weeks. Pre-, mid- and post-training resting ABP and BA FMD (exercised arm and non-exercised arm) were measured via automated brachial oscillometry and ultrasound respectively. BA FMD (normalized to the peak shear rate experienced in response to the reactive hyperaemic stimulus) remained unchanged [exercised arm, 0.029±0.003 to 0.026±0.003 to 0.029±0.004%/s−1 (pre- to mid- to post-training respectively); non-exercised arm, 0.023±0.003 to 0.023±0.003 to 0.024±0.003%/s−1 (pre- to mid- to post-training respectively); P=0.22]. In conclusion, improved systemic endothelial function is unlikely to be responsible for lowering arterial BP in this population.

scholarly journals Impaired popliteal artery flow-mediated dilation caused by reduced daily physical activity is prevented by increased shear stress

2017 ◽  
Vol 123 (1) ◽  
pp. 49-54 ◽  
Author(s):  
André L. Teixeira ◽  
Jaume Padilla ◽  
Lauro C. Vianna
Keyword(s):  
Physical Activity ◽  
Blood Flow ◽  
Shear Stress ◽  
Popliteal Artery ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Underlying Mechanism ◽  
Daily Physical Activity ◽  
Leg Blood Flow ◽  
Artery Flow

We recently showed that 5 days of reduced daily physical activity impair popliteal artery, but not brachial artery, flow-mediated dilation (FMD). However, the mechanisms by which physical inactivity causes leg vascular dysfunction are unclear. We reason that a reduction in leg blood flow-induced shear stress is a primary underlying mechanism by which reduced daily physical activity impairs popliteal artery FMD. Thus the purpose of this study was to determine whether increased leg blood flow and shear stress during inactivity prevent the reduction in popliteal artery FMD. Bilateral popliteal artery FMD measures were performed at baseline and after 5 days of a transition from high (>10,000 steps/day) to low levels (<5,000 steps/day) of physical activity in 13 healthy and physically active men [20 ± 2 (SD) yr]. During the inactive period, one foot was submerged in ~42°C water (i.e., heated leg) three times a day for 30 min each period, to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated leg). During heating, popliteal artery mean shear rate was increased in the heated leg (change of 119.3 ± 26.4%, P < 0.01) but slightly decreased in the nonheated leg (change of −21.8 ± 7.5%, P = 0.03). Popliteal artery FMD was impaired after 5 days of reduced daily physical activity in the control nonheated leg ( P < 0.01) but was unchanged in the heated leg ( P = 0.34). These results support the hypothesis that reduced leg blood flow-induced shear stress during physical inactivity is a key underlying mechanism mediating leg vascular dysfunction. NEW & NOTEWORTHY We found that the impairment in popliteal artery flow-mediated dilation caused by physical inactivity can be prevented by increased shear stress. These findings indicate that reduced leg blood flow-induced shear stress during physical inactivity may be a key underlying mechanism mediating the detrimental leg vascular effects of physical inactivity. Heating the foot area may be used as a nonpharmacological therapy to combat inactivity-induced leg vascular dysfunction, especially in people who are unable or unwilling to be active.

Interictal cerebral and systemic endothelial dysfunction in patients with migraine: a case–control study

2014 ◽  
Vol 86 (11) ◽  
pp. 1253-1257 ◽  
Author(s):  
Roopa Rajan ◽  
Dheeraj Khurana ◽  
Vivek Lal
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cerebral Artery ◽  
Breath Holding ◽  
Flow Mediated Dilation ◽  
Function Impairment ◽  
The Right ◽  
A Prospective Study ◽  
Artery Flow ◽  
Breath Holding Index

BackgroundAlthough systemic endothelial function is unimpaired in migraine, it is unknown whether cerebral endothelial function impairment exists in migraineurs.Materials and methodsWe conducted a prospective study to assess endothelial function in migraineurs (n=45) and healthy volunteers (n=44). Cerebral endothelial function was assessed by Breath Holding Index (BHI) on transcranial Doppler in bilateral middle cerebral artery (MCA at 30–60 mm), posterior cerebral artery (PCA at 60–80 mm) and basilar artery (BA at 80–120 mm) using bilateral monitoring probes fixed on headband. Brachial artery flow-mediated dilation (FMD) was used as measure of systemic endothelial function.ResultsThere was no difference in baseline mean velocities of MCA, PCA, BA among migraineurs and controls. Mean BHI was significantly lower in PCA (p<0.001) and BA (p<0.001) in patients with migraine with no difference in MCA (p=0.909, 0.450). Cerebral endothelial dysfunction (BHI<1.15) was present in 62.2% of migraineurs in the right PCA (p<0.001), 57.8% in left PCA (p<0.001) and 77.8% in BA (BHI <0.83, p<0.001). There was no difference in BHI among migraineurs without and with aura (n=15). Cerebral and systemic endothelial function had no correlation in migraineurs. Increasing BMI was identified as a predictor of impaired BHI in the BA in migraineurs (p=0.020). Age, sex, presence of aura, lateralisation of headache, headache frequency, time to last attack and impaired FMD were not associated with impaired PCA and BA BHI in migraineurs.ConclusionsMigraineurs may have isolated cerebral endothelial dysfunction restricted to the posterior circulation in the absence of systemic endothelial dysfunction.

Eight weeks of fish oil supplementation does not prevent sitting-induced leg endothelial dysfunction

2020 ◽  
Vol 45 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Takuma Morishima ◽  
Yosuke Tsuchiya ◽  
Jaume Padilla ◽  
Eisuke Ochi
Keyword(s):  
Blood Flow ◽  
Placebo Group ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Fish Oil ◽  
Popliteal Artery ◽  
Double Blind ◽  
Prolonged Sitting ◽  
Epa And Dha ◽  
Before And After

Prolonged sitting impairs leg endothelial function and this impairment is thought to be mediated by a sustained reduction in blood flow-induced shear stress. However, whether nutritional strategies can be used to prevent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that 8 weeks of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation would prevent endothelial dysfunction associated with sitting. Nineteen healthy men were randomly assigned to a placebo group or EPA+DHA group in a double-blind fashion. The EPA+DHA group was administered EPA-rich fish oil, containing 600 mg EPA and 260 mg DHA per day for 8 weeks. The placebo group received matching capsules for the same duration of time. Popliteal artery flow-mediated dilation (FMD) was measured at baseline and before and after a 3-h sitting period. During sitting, blood pressure, popliteal artery diameter, and blood velocity were measured every hour. Throughout the sitting period, popliteal artery blood flow and shear rate were markedly and similarly reduced in both groups (P < 0.05). However, counter to the hypothesis, 3 h of sitting impaired popliteal artery FMD to the same extent in both groups (P < 0.05). In conclusion, daily EPA and DHA supplementation is not effective at preventing the detrimental effects of prolonged sitting on leg endothelial function. Novelty We provide evidence that sitting-induced leg endothelial dysfunction in young healthy subjects cannot be remediated by a nutritional strategy known to produce cardiovascular benefits. This could be partially due to the low total dose of EPA and DHA administered.

scholarly journals Fluctuation in shear rate, with unaltered mean shear rate, improves brachial artery flow-mediated dilation in healthy, young men

2019 ◽  
Vol 126 (6) ◽  
pp. 1687-1693 ◽  
Author(s):  
Sophie M. Holder ◽  
Ellen A. Dawson ◽  
Áine Brislane ◽  
Jonny Hisdal ◽  
Daniel J. Green ◽  
...  
Keyword(s):  
Shear Stress ◽  
Shear Rate ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Negative Pressure ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Flow Mediated Dilation ◽  
Conduit Artery ◽  
Artery Flow

Increase in mean shear stress represents an important and potent hemodynamic stimulus to improve conduit artery endothelial function in humans. No previous study has examined whether fluctuations in shear rate patterns, without altering mean shear stress, impacts conduit artery endothelial function. This study examined the hypothesis that 30-min exposure to fluctuations in shear rate patterns, in the presence of unaltered mean shear rate, improves brachial artery flow-mediated dilation. Fifteen healthy men (27.3 ± 5.0 yr) completed the study. Bilateral brachial artery flow-mediated dilation was assessed before and after unilateral exposure to 30 min of intermittent negative pressure (10 s, −40mmHg; 7 s, 0 mmHg) to induce fluctuation in shear rate, while the contralateral arm was exposed to a resting period. Negative pressure significantly increased shear rate, followed by a decrease in shear rate upon pressure release (both P < 0.001). Across the 30-min intervention, mean shear rate was not different compared with baseline ( P = 0.458). A linear mixed model revealed a significant effect of time observed for flow-mediated dilation ( P = 0.029), with exploratory post hoc analysis showing an increase in the intervention arm (∆FMD +2.0%, P = 0.008), but not in the contralateral control arm (∆FMD +0.5%, P = 0.664). However, there was no effect for arm ( P = 0.619) or interaction effect ( P = 0.096). In conclusion, we found that fluctuations in shear patterns, with unaltered mean shear, improves brachial artery flow-mediated dilation. These novel data suggest that fluctuations in shear pattern, even in the absence of altered mean shear, represent a stimulus to acute change in endothelial function in healthy individuals. NEW & NOTEWORTHY Intermittent negative pressure applied to the forearm induced significant fluctuations in antegrade and retrograde shear rate, while mean shear was preserved relative to baseline. Our exploratory study revealed that brachial artery flow-mediated dilation was significantly improved following 30-min exposure to intermittent negative pressure. Fluctuations in blood flow or shear rate, with unaltered mean shear, may have important implications for vascular health; however, further research is required to identify the underlying mechanisms and potential long-term health benefits.

scholarly journals Sex does not influence impairments in popliteal endothelial-dependent vasodilator or vasoconstrictor responses following prolonged sitting

2019 ◽  
Vol 127 (3) ◽  
pp. 679-687 ◽  
Author(s):  
Myles W. O’Brien ◽  
Jarrett A. Johns ◽  
Tanner D. Williams ◽  
Derek S. Kimmerly
Keyword(s):  
Endothelial Function ◽  
Popliteal Artery ◽  
Young Men ◽  
Low Flow ◽  
Flow Mediated Dilation ◽  
Vascular Effects ◽  
Acute Bout ◽  
Men And Women ◽  
Prolonged Sitting ◽  
Before And After

An acute bout of prolonged sitting (PS) impairs the popliteal artery flow-mediated dilation (FMD) response. Despite equivocal reductions in mean shear rate, young women demonstrate an attenuated decline in popliteal FMD versus young men. However, it is uncertain whether popliteal endothelial-dependent vasoconstrictor responses [low-flow-mediated constriction (L-FMC)] are similarly affected by PS and/or whether sex differences exist. We tested the hypothesis that women would have attenuated reductions in both popliteal FMD and L-FMC responses following an acute bout of PS. Popliteal FMD and L-FMC responses were assessed via duplex ultrasonography before and after a 3-h bout of PS. These responses were then compared between 10 men (24 ± 2 yr) and 10 women (23 ± 2 yr) with similar ( P > 0.13) levels of objectively measured habitual physical activity (via PiezoRx) and sedentary time (via activPAL). At baseline, men and women exhibited similar ( P > 0.46) popliteal FMD (4.8 ± 1.2 vs. 4.5 ± 0.6%) and L-FMC (–1.7 ± 1.0 vs. –1.9 ± 0.9%) responses. Both sexes experienced identical (group: P > 0.76; time: P < 0.001) PS-induced impairments in popliteal FMD (–2.8 ± 1.4 vs. –2.6 ± 0.9%) and L-FMC (1.3 ± 0.7% vs. 1.4 ± 0.7%). In young adults, sex did not influence the negative PS-induced FMD, L-FMC, or microvascular responses in the lower limb. As such, our findings suggest that young men and women are similarly susceptible to the acute negative vascular effects of PS. Future studies should extend these findings to older, less physically active adults and/or patients with vascular disease. NEW & NOTEWORTHY We compared changes in popliteal artery endothelial function to a single 3-h bout of sitting between young men and women. Both groups exhibited similar endothelial-dependent vasodilation (i.e., flow-mediated dilation) and endothelial-dependent vasoconstrictor responses (i.e., low-flow-mediated constriction) at baseline and equivocal impairments in these measures of endothelial function following prolonged sitting. These findings demonstrate that acute impairments in conduit artery endothelial health associated with uninterrupted sitting are not influenced by sex in young, healthy adults.

Abstract 319: Effects of Muscle Stretching on Flow-Mediated Dilation of Popliteal Artery in Patients With Peripheral Artery Disease

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kazuki Hotta ◽  
Wayne B Batchelor ◽  
James Graven ◽  
Vishal Dahya ◽  
Thomas E Noel ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Popliteal Artery ◽  
Calf Muscle ◽  
Walking Distance ◽  
Flow Mediated Dilation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Peripheral Artery ◽  
Muscle Stretching ◽  
Artery Disease

Patients with peripheral artery disease (PAD) frequently have walking impairment due to lower extremity claudication. Our preliminary results in a rat model of aging indicate that a program of daily calf muscle stretching improves endothelium-dependent dilation of soleus muscle arterioles and increases soleus muscle blood flow during exercise. However, the effects of muscle stretching on the function of arteries supplying the legs of PAD patients is unknown. We hypothesized that daily calf muscle stretching improves vascular endothelial function and walking distance in PAD patients. To test our hypothesis, a randomized, non-blinded, crossover study was performed. Four weeks of muscle stretching (30 min/d, 5 days/wk) and 4 weeks of sedentary lifestyle (no stretching) were performed in random order. Thirteen patients with PAD participated in this study (71 ± 2 years old; 7 males and 6 females). During the stretching intervention both ankle joints were maintained at 15o of dorsiflexion using ankle dorsiflexion splints to stretch their calf muscles at home. Flow-mediated dilation (FMD; dilation to post-occlusion reactive hyperemia) and nitroglycerin-induced dilation (dilation to sublingual 0.4 mg nitroglycerin) of the popliteal artery were measured after 4 weeks of muscle stretching and after the no stretching period using ultrasound. A six-minute walk test was also performed to obtain walking distance. After 4 weeks of muscle stretching, FMD and 6-minute walking distance significantly improved as compared to the values measured after 4 weeks of no stretching (FMD: 5.2 ± 0.6 % vs. 3.7 ± 0.4 %, P=0.003 stretching vs. no stretching, 6-minute walking distance: 355 ± 32 m vs. 311 ± 31 m, P=0.007, stretching vs. no stretching; mean ± SE). No difference in nitroglycerin-induced dilation was found between groups (10.9 ± 1.4 vs. 9.9 ± 1.1 %, P=0.54, stretching vs. no stretching). Percentage change of walking distance (%change = [(stretching - no stretching) / no stretching] x 100) significantly correlated with the %change of FMD (R 2 =0.65, P=0.03). These results indicate that static calf muscle stretching enhances vascular endothelial function of the popliteal artery, contributing to improvement of walking tolerance in PAD patients.

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