Evidence of a limb- and shear stress stimulus profile-dependent impact of high-intensity cycling training on flow-mediated dilation

2020 ◽  
Vol 45 (2) ◽  
pp. 135-145
Author(s):  
Trevor J. King ◽  
Kyra E. Pyke

Lower limb endurance training can improve conduit artery flow-mediated dilation (FMD) in response to transient increases in shear stress (reactive hyperemia; RH-FMD) in both the upper and lower limbs. Sustained increases in shear stress recruit a partially distinct transduction pathway and elicit a physiologically relevant FMD response (SS-FMD) that provides distinct information regarding endothelial function. However, the impact of training on SS-FMD is not well understood. The purpose of this study was to determine the impact of cycling training on handgrip exercise-induced brachial artery (BA) FMD (BA SS-FMD) and calf plantar-flexion-induced superficial femoral artery (SFA) FMD (SFA SS-FMD). RH-FMD was also assessed in both arteries. Twenty-eight young males were randomized to control (n = 12) or training (n = 16) groups. The training group cycled 30 min/day, 3 days/week for 4 weeks at 80% heart rate reserve. FMD was assessed in the BA and SFA before and after the intervention via Duplex ultrasound. Results are means ± SD. Training did not impact SS-FMD in either artery, and SFA RH-FMD was also unchanged (p > 0.05). When controlling for the shear rate stimulus via covariate analysis, BA RH-FMD improved in the training group (p = 0.05) (control – pre-intervention: 5.7% ± 2.4%, post-intervention: 5.3% ± 2.4%; training – pre-intervention: 5.4% ± 2.5%, post-intervention: 7.2% ± 2.4%). Thus, endurance training resulted in nonuniform adaptations to endothelial function, with an isolated impact on the BA’s ability to transduce a transient increase in shear stress. Novelty Training did not alter SS-FMD in the arm or leg. RH-FMD was augmented in the arm only. Thus training adaptations were limb- and shear stress profile-specific.

Author(s):  
Rakhbeer Singh Boparai ◽  
Rachel J Skow ◽  
Sauleha Farooq ◽  
Craig D Steinback ◽  
Margie H Davenport

We assessed the impact of a structured lower-limb aerobic exercise training intervention during pregnancy on brachial artery endothelial function, shear rate and patterns, and forearm blood flow and reactive hyperemia. Twenty-seven pregnant women were recruited and randomized into either a control group (n=11; 31.0 ± 0.7 years), or an exercise intervention group (n=16; 32.6 ± 0.9 years; NCT02948439). The exercise group completed 40 minutes of aerobic exercise (50-70% heart rate reserve) 3-4 times per week, between the second and third trimester of pregnancy. Endothelial function was assessed using flow-mediated dilation (FMD, normalized for shear stress) pre- (16-20 weeks) and post-intervention (34-36 weeks). The exercise training group experienced an attenuated increase in mean arterial pressure (MAP) relative to the control group (∆MAP exercise: +2± 2 mmHg vs. control: +7±3 mmHg; p=0.044) from pre- to post-intervention. % FMD change corrected for shear stress was not different between groups (p=0.460); however, the post occlusion mean flow rate (exercise: 437±32 mL/min vs. control: 364±35 mL/min; p=0.001) and post occlusion anterograde flow rate (exercise: 438±32 mL/min vs. control: 364±46 mL/min;p=0.001) were larger for the exercise training group compared to controls, post-intervention. Although endothelial function was not different between groups, we observed an increase in microcirculatory dilatory capacity, as suggested by the augmented reactive hyperemia in the exercise training group. Novelty: • Endothelial function was not altered with exercise training during pregnancy. • Exercise training did contribute to improved cardiovascular outcomes, which may have been associated with augmented reactive hyperaemia, indicative of increased microcirculatory dilatory capacity


2019 ◽  
Vol 126 (2) ◽  
pp. 314-321 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Taylor V. Stimpson ◽  
Kyra E. Pyke

Acutely imposed oscillatory shear stress (OSS) reduces reactive hyperemia flow-mediated dilation (RH-FMD) in conduit arteries of men; however, whether a similar impairment occurs in women or with FMD in response to a controlled, sustained shear stress stimulus (SS-FMD) is unknown. The purpose of this study was to determine the impact of OSS on RH-FMD and SS-FMD in men and women. OSS was provoked in the brachial artery using a 30-min forearm cuff inflation (70 mmHg). Healthy men [ n = 16, 25 yr (SD 3)] and women [ n = 16, 21 yr (SD 2)] completed the OSS intervention twice (separate days). Brachial artery endothelial function was assessed pre- and postintervention via either RH-FMD or 6 min of handgrip SS-FMD using Duplex ultrasound. The RH-FMD stimulus was calculated as shear rate area under the curve 60 s postdeflation (SRAUC60), whereas SS-FMD shear rate was targeted to produce a similar stimulus pre- and postintervention. The OSS intervention decreased RH-FMD in both sexes [men: 6.2% (SD 3.4) to 5.2% (SD 3.0); women: 5.4% (SD 2.0) to 3.1% (SD 1.8), P < 0.001), although this was accompanied by a reduced SRAUC60. There was no significant effect of the intervention on RH-FMD with SRAUC60 as a covariate ( P = 0.310). Handgrip exercise elicited a similar stimulus before and after the intervention ( P = 0.287) in men and women ( P = 0.873). Men demonstrated blunted SS-FMD [4.8% (SD 1.9) to 3.2% (SD 1.9), P < 0.001], whereas women displayed preserved SS-FMD following the intervention [3.5% (SD 1.9) to 4.0% (SD 1.9), P = 0.061]. The lower SS-FMD in men but not women following OSS provides evidence of sex differences in the effects of OSS on conduit artery endothelial function. NEW & NOTEWORTHY Acute exposure to oscillatory shear stress induces transient endothelial dysfunction in men; however, whether women experience similar impairments is unknown. Following acutely imposed oscillatory shear stress, there was a decrease in flow-mediated dilation stimulated by a physiologically relevant sustained increase in shear stress in men but not in premenopausal women. These findings demonstrate, for the first time in humans that there are sex differences in the impact of oscillatory shear stress on endothelial function.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Stella Brilli ◽  
Dimitris Tousoulis ◽  
Charalambos Antoniades ◽  
George Hatzis ◽  
Nikos Ioakeimidis ◽  
...  

Background: Marfan syndrome is characterised by high risk of aortic dissections and increased cardiovascular risk. However, the impact of Marfan syndrome on endothelial function and arterial stiffness is unclear, while the role of matrix metalloproteinases is unknown. We examined the impact of Marfan syndrome on the elastic properties of the arterial tree, and vascular endothelial function, and we evaluated the potential role of matrix metalloproteinases in these effects. Methods: The study population consisted of 17 subjects with Marfan syndrome, aged 26.6±2.3 years old, with BMI 20.5±1.03Kg/m2 and 22 healthy individuals matched for gender, age (26.4±0.78 years old, p=NS) and BMI (22.4±0.86 Kg/m2). Arterial stiffness was evaluated by measuring carotid-femoral pulse wave velocity (PWV), while augmentation pressure and augmentation index (AIx) were also determined, as measures of arterial wave reflections. Endothelial function was evaluated by determining flow mediated dilation (FMD) in the brachial artery while matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA. Results: Patients with Marfan syndrome had significantly lower pulse pressure in the radial artery (41.0±1.07mmHg) compared to controls (51.3±4.4mmHg). In addition, patients had higher AIx (17.6±2.4%) and augmentation pressure (5.44±0.65mmHg) compared to controls (7.72±3.43% and 2.41±1.14mmHg respectively, p<0.05 for both). However, the difference in PWV between patients and controls did not reach statistical significance (6.33±0.33 vs 5.96±0.23m/s respectively, p=NS). Patients with Marfan syndrome had lower FMD (2.05±1.13%) and higher plasma MMP-9 (827±70ng/ml) compared to controls (6.8±2.3% p<0.05 and 326±50ng/ml, p<0.01). Conclusions: Marfan syndrome is associated with increased MMP-9 levels, as well as with elevated augmentation index and augmentation pressure compared to healthy individuals, matched for age, gender and body mass index. Moreover, flow-mediated dilation is also impaired in these subjects. These findings suggest that Marfan syndrome directly affects the elastic properties and endothelial function of the arterial tree, with matrix metalloproteinases being important mediators in the pathophysiology of this syndrome.


2020 ◽  
Vol 41 (33) ◽  
pp. 3144-3152 ◽  
Author(s):  
Boris Schnorbus ◽  
Andreas Daiber ◽  
Kerstin Jurk ◽  
Silke Warnke ◽  
Jochem Koenig ◽  
...  

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P &lt; 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73


Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 241-251
Author(s):  
Sarah C. Couch ◽  
Brian E. Saelens ◽  
Philip R. Khoury ◽  
Katherine B. Dart ◽  
Kelli Hinn ◽  
...  

This randomized control trial assessed the post-intervention and 18-month follow-up effects of a 6-month dietary approaches to stop hypertension (DASH)-focused behavioral nutrition intervention, initiated in clinic with subsequent telephone and mail contact, on blood pressure (BP) and endothelial function in adolescents with elevated BP. Adolescents (n=159) 11 to 18 years of age with newly diagnosed elevated BP or stage 1 hypertension treated at a hospital-based clinic were randomized. DASH participants received a take-home manual plus 2 face-to-face counseling sessions at baseline and 3 months with a dietitian regarding the DASH diet, 6 monthly mailings, and 8 weekly and then 7 biweekly telephone calls focused on behavioral strategies to promote DASH adherence. Routine care participants received nutrition counseling with a dietitian consistent with pediatric guidelines established by the National High Blood Pressure Education Program. Outcomes, measured pre- and post-intervention and at 18-months follow-up, included change in BP, change in brachial artery flow-mediated dilation, and change in DASH score based on 3-day diet recalls. Adolescents in DASH versus routine care had a greater improvement in systolic BP (–2.7 mm Hg, P = 0.03, –0.3 z-score, P =0.03), flow-mediated dilation (2.5%, P =0.05), and DASH score (13.3 points, P <0.0001) from baseline to post-treatment and a greater improvement in flow-mediated dilation (3.1%, P =0.03) and DASH score (7.4 points, P =0.01) to 18 months. The DASH intervention proved more effective than routine care in initial systolic BP improvement and longer term improvement in endothelial function and diet quality in adolescents with elevated BP and hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00585832.


2016 ◽  
Vol 310 (5) ◽  
pp. H648-H653 ◽  
Author(s):  
Robert M. Restaino ◽  
Lauren K. Walsh ◽  
Takuma Morishima ◽  
Jennifer R. Vranish ◽  
Luis A. Martinez-Lemus ◽  
...  

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.


2010 ◽  
Vol 39 (3) ◽  
pp. 222-231 ◽  
Author(s):  
Denise C. Cooper ◽  
Milos S. Milic ◽  
Paul J. Mills ◽  
Wayne A. Bardwell ◽  
Michael G. Ziegler ◽  
...  

2014 ◽  
Vol 39 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Ingrid C. Szijgyarto ◽  
Veronica J. Poitras ◽  
Brendon J. Gurd ◽  
Kyra E. Pyke

Exercise elevates conduit artery shear stress and stimulates flow-mediated dilation (FMD). However, little is known regarding the impact of acute psychological and physical stress on this response. The purpose of this study was to examine the impact of the Trier Social Stress Test (TSST (speech and arithmetic tasks)) and a cold pressor test (CPT) with and without social evaluation (SE) on exercise-induced brachial artery FMD (EX-FMD). A total of 59 healthy male subjects were randomly assigned to 1 of 3 conditions: TSST, CPT, or CPT with SE. During 6 min of handgrip exercise, brachial artery EX-FMD was assessed before and 15 and 35 min poststress with echo and Doppler ultrasound. Shear stress was estimated as shear rate, calculated as brachial artery mean blood velocity/brachial artery diameter. Results are means ± SD. All conditions elicited significant physiological stress responses. Salivary cortisol increased from 4.6 ± 2.4 nmol/L to 10.0 ± 5.0 nmol/L (p < 0.001; condition effect: p = 0.292). Mean arterial pressure increased from 98.6 ± 12.1 mm Hg to 131.9 ± 18.7 mm Hg (p < 0.001; condition effect: p = 0.664). Exercise shear rate did not differ between conditions (p = 0.592), although it was modestly lower poststress (prestress: 72.3 ± 4.5 s−1; 15 min poststress: 70.8 ± 5.4 s−1; 35 min poststress: 70.6 ± 6.1 s−1; trial effect: p = 0.011). EX-FMD increased from prestress to 15 min poststress in all conditions (prestress: 6.2% ± 2.8%; 15 min poststress: 7.9% ± 3.2%; 35 min poststress: 6.6% ± 2.9%; trial effect: p < 0.001; condition effect: p = 0.611). In conclusion, all conditions elicited similar stress responses that transiently enhanced EX-FMD. This response may help to support muscle perfusion during stress.


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