Brachial Artery Shear Rate Research Articles

Similar endothelium-dependent vascular responses to intermittent hypoxia in young and older adults.

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults.NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Brachial Artery Shear Rate Responses To Sprint Efforts And Moderate Intensity Cycling

Brachial Artery Shear Rate Responses To Sprint Efforts And Moderate Intensity Cycling

Brachial artery flow-mediated dilation during incremental handgrip exercise is not impacted by sex or female sex hormones

Sex differences exist in reactive hyperemia flow-mediated dilation (RH-FMD), with males demonstrating larger RH-FMD responses than naturally menstruating females and females using oral contraception (OC). This difference is thought to be partly attributed to sex hormones. Among females, some studies demonstrate lower RH-FMD in females using OC relative to naturally menstruating females. To date, non-invasive assessments of endothelial function in males, naturally cycling females and females using OC have only been completed using RH-FMD. Notably, due to differences in the shear stimulus during sustained shear-induced FMD (SS-FMD) versus the transient pattern observed with RH-FMD, SS-FMD may provide distinct insight into endothelial dysfunction undetected with RH-FMD. Therefore, we hypothesized that the SS-FMD responses to incremental handgrip (IHG) exercise would be greatest in males, and that females using OC would have the smallest increase in SS-FMD compared to males and naturally menstruating females. The IHG protocol consisted of 3-minute stages of rhythmic handgrip exercise at 15, 30, and 45% of an individual’s maximal voluntary contraction (MVC) force, with no rest period between MVC transitions. Brachial artery diameter and blood velocity were measured simultaneously via duplex Doppler ultrasound in 10 males (26±4 [mean±SD] years), 11 naturally menstruating females (25±4 years), and 9 females using OC (27±5 years) during IHG. Females were tested in the mid-luteal (ML) and active (high hormone) OC phases. SS-FMD and shear rate were analyzed using linear mixed model analyses. MVC was greater in males relative to both groups of females (males: 40±6, ML: 28±8, OC: 26±6 kg; One-way ANOVA: post-hocs P≤0.001). Brachial artery shear rate was not different between males, ML females or females using OC throughout exercise (group-by-stage interaction: P=0.975). Consequently, the brachial artery dilated by 1.3±1.5, 0.1±2.1, and 1.2±3.6 % at 15% MVC, 4.0±3.1, 2.7±3.3, and 4.1±4.8 % at 30% MVC, and 9.1±4.9, 7.3±5.4, and 7.6±5.9 % at 45% MVC, in males, ML females, and females using OC, respectively (all P>0.05). Furthermore, the slopes of the relationship between the change in brachial artery diameter and shear rate was similar between the three groups (Males: 0.0004±0.0002, ML: 0.0003±0.0002, OC: 0.0003±0.0002 Δmm/Δ1·s -1 ; One-way ANOVA: P=0.564). Taken together, these data indicate that endothelial function in response to sustained elevations in shear stress are not impacted by biological sex or OC use. Supported by the Natural Sciences and Engineering Research Council of Canada, and IEEM indirect funds. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The impact of age on the vascular response to acute sauna exposure

Passive heat exposure has been shown to be a promising method to improve endothelial health. Sauna usage specifically, has been linked to reduced risk of cardiovascular disease in young and middle-aged populations. Increases in blood flow and shear rates associated with heat exposure are often considered to have a major influence on the observed improved endothelial function following repeated heat exposure; however, the magnitude of these shear and flow responses may potentially vary with age or starting endothelial function. Purpose: The purpose of this study was to determine if the vascular response to acute sauna heating is similar between healthy young and middle-aged adults and if the response is related to baseline endothelial function. Methods: 10 young (24.9 ± 4.2 years, 6 male and 4 female) and 8 middle aged adults (55.6 ± 3.9 years 4 males and 4 females) underwent 40 min of sauna exposure at 80ºC. Esophageal temperature was recorded throughout the duration of the experiment. Brachial artery flow-mediated dilation (FMD) blood flow, artery diameter, shear rates and blood pressure were recorded at baseline and following heat exposure. Results: The increase in core temperature (Tc) followed similar trends in both the young and middle-aged adults (young ΔTc = 1.386 ± 0.52 ºC vs middle-Age Δ Tc = 1.637 ± 0.56 ºC). Heat-induced brachial artery dilation and brachial artery shear rate also increased similarly in both age groups (young Δ diameter = 0.048 ± 0.022 cm vs middle-age Δ diameter = 0.074 ± 0.036 cm, young Δ shear = 164.5± 106.8 sec- 1 vs middle-age Δ shear = 150.3 ± 56.29 sec -1 ). Heat induced dilation was strongly correlated to baseline endothelial function in the young (r = 0.86, P=0.006). This relationship was not observed in the brachial artery of middle-aged adults (r = 0.257, P=0.539). Systolic blood pressure (SBP) was significantly reduced following sauna in the middle-aged participants from 135.25 ± 17.50 mmHg to 122.38 ± 19.7 mmHg (P=0.017). There was a slight elevation in SBP following sauna in the young participants from 119.4 ± 6.38 mmHg to 123.1 ± 7.65 mmHg (P=0.017). Diastolic blood pressure (DBP) was significantly reduced in both age groups (P<0.001) with middle age seeing greater reductions (P=0.05) from 80.63 ± 10.97 mmHg to 69.75 ± 8.41 mmHg vs the young 71.2 ± 8.24 mmHg to 66.9 ± 4.56 mmHg. Conclusion: Young and middle-aged adults have similar changes in shear rate and brachial artery dilation in response to acute sauna heating, but the middle-aged adults exhibit significantly greater decreases in SBP and DBP than young adults. In young adults, endothelial function is strongly correlated to heat induced dilation in the brachial artery. This relationship is not present in the middle age population suggesting that heat-induced dilation may rely on mechanisms other than endothelial function in middle-aged adults. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of exercise during water immersion on arterial function in humans.

Flow-mediated dilation (FMD) provides a valid bioassay of vascular function in humans. Although water immersion induces hemodynamic effects that modify brachial artery shear stress, it is unclear whether water-based exercise modifies FMD. We hypothesized that exercise in 32°C water would decrease brachial artery shear and FMD relative to land-based exercise, whereas exercise in 38°C would increase brachial shear and FMD. Ten healthy participants (8 males; 23.9 ± 3.3 yr) completed 30 min of resistance-matched cycle exercise in three separate conditions: on land and in 32°C and 38°C water. Brachial artery shear rate area under the curve (SRAUC) was measured throughout each condition, with FMD measured pre- and postexercise. Brachial SRAUC increased during exercise in all conditions and was highest across the 38°C condition compared with Land and 32°C conditions (38°C: 27,507 ± 8,350 vs. Land: 9,908 ± 4,738 vs. 32°C: 13,840 ± 5,861 1/s, P < 0.001). Retrograde diastolic shear was greater during 32°C than both Land and 38°C conditions (32°C:-3,869 ± 2,198 vs. Land:-1,602 ± 1,334 vs. 32°C:-1,036 ± 1,754, P < 0.01). FMD increased as a result of 38°C (6.2 ± 1.9 vs. 8.5 ± 2.7%, P = 0.03), with no change in the Land exercise (6.3 ± 2.4 vs. 7.7 ± 2.4%, P = 0.10) or 32°C condition (6.4 ± 3.2 vs. 6.7 ± 3.2%, P = 0.99). Our findings indicate that cycle exercise in hot water attenuates retrograde shear, increases antegrade shear, and FMD. Exercise in 32°C water induces central hemodynamic changes relative to land-based exercise, but these do not translate to increases in FMD in either condition, likely due to the impact of increased retrograde shear. Our findings indicate that modification of shear has direct acute impacts on endothelial function in humans.

Comparing the Effects of 30‐ and 60‐min of Acute Whole‐Body Passive Heat Stress on Peripheral Vascular Function in Older Adults

IntroductionMacro‐ and microvascular dysfunction elevate the risk of cardiovascular disease (CVD). Heat therapy has the potential to improve vascular health and reduce CVD risk, but the optimal length of heat stress exposure is unknown. We hypothesized that 1) acute whole body heat stress (WBHS) would increase vascular function and 2) a longer WBHS period (30‐ vs 60‐min) would elicit a greater effect.Methods20 older adults (10 female; 64±7 y) underwent two separate periods of WBHS (30‐ vs 60‐min) via water perfused suit (48°C) in a randomized, counterbalanced design. Macrovascular function via flow‐mediated dilation (FMD) and microvascular function via skin reactive hyperemia (SKBF RH) were assessed before (PRE) and after (POST) WBHS. Core (Tcore; rectal) and skin (Tskin; 6‐site average) temperatures were monitored throughout. Repeated measures ANOVA were used to assess the effect of time (PRE vs POST) and visit (30‐ vs 60‐min) on all outcomes.ResultsTcore and Tskin increased after both WBHS periods (Tcore: 30‐min, PRE: 36.4±0.3, POST: 36.6±0.3°C; 60‐min, PRE: 36.4±0.3, POST: 36.8±0.2°C, p=0.001; Tskin: 30‐min, PRE: 33.5±0.6, POST: 36.3±0.4°C, p&lt;0.0005; 60‐min, PRE: 33.2±0.5°C, POST: 36.6±0.5°C, p&lt;0.0005). FMD% was unchanged (30‐min, PRE: 8.5±5.1%, POST: 7.1±4.2%; 60‐min, PRE: 7.7±3.9%, POST: 6.6±4.3%; p=0.10) after both WBHS periods. During RH, brachial artery shear rate area under the curve was higher after 30‐ (PRE: 17.08±9.57, POST: 26.34±13.06·10‐3 AUC; p=0.003) but not 60‐min (PRE: 21.06±12.30, POST: 27.83±19.32·10‐3 AUC; p=0.186). Total SKBFAUC increased following both 30‐ (PRE: 6.31±3.22, POST: 12.82±6.44·10‐3 AUC; p&lt;0.0005) and 60‐min (PRE: 6.01±3.24, POST: 9.609±4.882·10‐3 AUC; p=0.037), whereas peak SKBF fluxAUC increased following 30‐ (PRE: 1.86±1.54, POST: 4.15±3.07·10‐3 AUC; p=0.001) but not 60‐min (PRE: 1.58±1.31, POST: 2.93±2.77·10‐3 AUC; p=0.1113) of WBHS.DiscussionUp to 60‐min of acute WBHS does not change macrovascular function in older adults. Interestingly, WBHS might increase downstream microvascular functional capacity. The changes in microvascular function following 30‐min of WBHS may reflect early markers of the benefits of repeated whole body heat stress.

Shear‐thinning behaviour of blood in response to active hyperaemia: Implications for the assessment of arterial shear stress‐mediated dilatation

What is the central question of this study? Quantitative values of shear rate-specific blood viscosity and shear stress in the human macrovasculature in response to exercise hyperaemia are unknown. What is the main finding and its importance? Using the handgrip exercise model, we showed that an increase in brachial artery shear rate led to a decrease in blood viscosity, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in brachial artery shear stress based on shear rate prediction. Our data yield new insights into the magnitude and regulation of macrovascular blood viscosity and shear stress in physiological conditions of elevated metabolic demand and blood flow in humans. Blood viscosity is a well-known determinant of shear stress and vascular resistance; however, accurate quantitative assessments of shear rate-specific blood viscosity in the macrovasculature in conditions of elevated blood flow are inherently difficult, owing to the shear-thinning behaviour of blood. Herein, 12 men performed graded rhythmic handgrip exercise at 20, 40, 60 and 80% of their maximal workload. Brachial artery shear rate and diameter were measured via high-resolution Duplex ultrasound. Blood was sampled serially from an i.v. cannula in the exercising arm for the assessment of blood viscosity (cone-plates viscometer). We measured ex vivo blood viscosity at 10 discrete shear rates within the physiological range documented for the brachial artery in basal and exercise conditions. Subsequently, the blood viscosity data were fitted with a two-phase exponential decay, facilitating interpolation of blood viscosity values corresponding to the ultrasound-derived shear rate. Brachial artery shear rate and shear stress increased in a stepwise manner with increasing exercise intensity, reaching peak values of 940±245s-1 and 3.68±0.92Pa, respectively. Conversely, brachial artery shear rate-specific blood viscosity decreased with respect to baseline values throughout all exercise intensities by ∼6-11%, reaching a minimal value of 3.92±0.35mPas, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in shear stress based on shear rate prediction. Consequently, the use of shear stress yielded a higher slope for the brachial artery stimulus versus dilatation relationship than shear rate. Collectively, our data refute the use of shear rate to infer arterial shear stress-mediated processes.

Examining the acute effects of retrograde versus low mean shear rate on flow-mediated dilation.

Arterial endothelial function is acutely and chronically regulated by blood flow-associated shear stress. An acute intervention employing modest forearm cuff occlusion to simultaneously increase retrograde and decrease mean brachial artery shear rate for 30 min evokes transient impairments in flow-mediated dilation (FMD). However, the independent influence of the low mean versus the retrograde shear stress components is unclear. Healthy young adults [n = 24 (12 women, 12 men); 22 ± 2 yr, body mass index = 25 ± 2 kg/m2 (mean ± SD)] completed three laboratory visits within 1 wk. Visits consisted of 45 min of supine rest followed by a brachial artery FMD test (duplex ultrasound) before and after a 30-min intervention: control (shear rate unchanged), cuff (mean shear rate decreased, retrograde shear rate increased), or arterial compression (mean shear rate decreased, no increase in retrograde shear rate). The mean shear rate on the compression visit was targeted to match that achieved on the cuff visit. Cuff and compression trials decreased mean shear rate to a similar extent (cuff: 43 ± 22 s-1, compression: 43 ± 21 s-1; P = 0.850) compared with control (65 ± 21 s-1; both P < 0.001), with the retrograde component elevated only in the former (cuff: -83 ± 30 s-1, compression: -7 ± 5 s-1; P < 0.001). FMD decreased by 29 ± 30% (P < 0.001) after the cuff intervention and 32 ± 24% (P < 0.001) after the compression trial but was unchanged on the control visit (-0.3 ± 18%; P = 0.754). This was not altered by accounting for the shear rate stimulus. An increased retrograde shear stress does not appear to be obligatory for the transient reduction in FMD achieved after a 30-min exposure to low mean shear stress. These findings provide novel mechanistic insight on the regulation of endothelial function in vivo. NEW & NOTEWORTHY Low mean and retrograde shear stress are considered atherogenic; however, their relative contribution to the acute regulation of endothelial function in humans is unclear. Matched reductions in mean shear stress (30 min), with and without increases in retrograde shear stress, elicited equivalent reductions in flow-mediated dilation in men and women. These findings afford novel insight regarding the shear stress components governing the acute (dys)regulation of conduit artery endothelial function in vivo.

Cardiovascular Responses to Dynamic Handgrip Exercise in Patients with Heart Failure with Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with symptoms of exercise intolerance, which may correspond to disease‐related changes in the peripheral circulation. A small muscle mass (dynamic handgrip, HG) exercise that evokes minimal cardiopulmonary stress was utilized to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium‐dependent vasodilation in patients with HFpEF compared to hypertensive controls (CON).MethodsWe evaluated heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and brachial artery blood velocity and diameter in CON (n = 25, 52 ± 7 y, BMI 30 ± 6 kg/m2) and patients with HFpEF (n = 25, 69 ± 10 y, BMI 33 ± 6 kg/m2) during dynamic HG exercise (15, 30, and 45% MVC, 1 contraction/sec). Brachial artery blood flow and vascular conductance were determined to quantify the hemodynamic response to HG exercise, and changes in brachial artery diameter were evaluated to assess conduit vessel vasodilatory capacity.ResultsWhile HR modestly increased in both groups at 45% MVC (10 ± 2 and 8 ± 2 bpm compared to rest, HFpEF and Control), SV and CO were unchanged across exercise intensities in both groups. Brachial artery blood flow was similar between groups at the lowest exercise intensity (15% MVC: 145 ± 41 vs. 158 ± 17 ml/min, HFpEF vs. CON) but was blunted by 20–40% in HFpEF patients at higher work rates (30% MVC: 229 ± 8 vs. 274 ± 23 ml/min, 45% MVC: 283 ± 17 vs. 399 ± 34 ml/min, HFpEF vs. CON). Brachial artery vascular conductance increased to a similar degree in both groups at 15 and 30% MVC, but was blunted by ~20% at the highest exercise intensity (45% MVC: 2.74 ± 0.21 vs. 3.54 ± 0.30 ml/min/mmHg, HFpEF vs. CON). Brachial artery shear rate was similar between HFpEF and CON at all exercise intensities. Brachial artery diameter increased across work rates in both HFpEF (15% MVC: 3 ± 1%, 30% MVC: 6 ± 1%, 45% MVC: 8 ± 1%) and CON (15% MVC: 2 ± 1%, 30% MVC: 4 ± 1%, 45% MVC: 7 ± 1%), and there was no difference between groups.ConclusionsThese results provide evidence for impaired skeletal muscle blood flow during small muscle mass exercise in patients with HFpEF that cannot be attributed to a disease‐related alteration in central hemodynamics. However, brachial artery vasodilation in response to the step‐wise, sustained shear stimulus evoked during exercise was similar between groups, suggesting a preservation of endothelium‐dependent dilation in patients with HFpEF compared to their hypertensive counterparts. Together, these findings suggest an overall derangement in the regulation of muscle blood flow during exercise in patients with HFpEF that is not attributable to disease‐related changes in endothelial function.Support or Funding InformationThis project is funded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001697, RX001418, E6910R).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Age and Aerobic Exercise Training on Conduit Artery Wall Thickness: Role of the Shear Pattern

Hemodynamic shear stress is the frictional force of blood on the arterial wall. The shear pattern in the conduit artery affects the endothelium and may participate in the development and progression of atherosclerosis. We investigated the role of the shear pattern in age- and aerobic exercise-induced changes in conduit artery wall thickness via cross-sectional and interventional studies. In a cross-sectional study, we found that brachial shear rate patterns and brachial artery intima-media thickness (IMT) correlated with age. Additionally, brachial artery shear rate patterns were associated with brachial artery IMT in 102 middle-aged and older individuals. In an interventional study, 39 middle-aged and older subjects were divided into 2 groups: control and exercise. The exercise group completed 12 weeks of aerobic exercise training. Aerobic exercise training significantly increased the antegrade shear rate and decreased the retrograde shear rate and brachial artery IMT. Moreover, changes in the brachial artery antegrade shear rate and the retrograde shear rate correlated with the change in brachial artery IMT. The results of the present study indicate that changes in brachial artery shear rate patterns may contribute to age- and aerobic exercise training-induced changes in brachial artery wall thickness.

Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells

The effect of endurance exercise on circulating microvesicle dynamics and their impact on surrounding endothelial cells is unclear. Here we tested the hypothesis that exercise intensity modulates the time course of platelet (PMV) and endothelial-derived (EMV) microvesicle appearance in the circulation through hemodynamic and biochemical-related mechanisms, and that microvesicles formed during exercise would stimulate endothelial angiogenesis in vitro. Nine healthy young men had venous blood samples taken before, during, and throughout the recovery period after 1 h of moderate [46 ± 2% maximal oxygen uptake (V̇o2max)] or heavy (67 ± 2% V̇o2max) intensity semirecumbent cycling and a time-matched resting control trial. In vitro experiments were performed by incubating endothelial cells with rest and exercise-derived microvesicles to examine their effects on cell angiogenic capacities. PMVs (CD41+) increased from baseline only during heavy exercise (from 21 ± 1 × 103 to 55 ± 8 × 103 and 48 ± 6 × 103 PMV/μl at 30 and 60 min, respectively; P < 0.05), returning to baseline early in postexercise recovery (P > 0.05), whereas EMVs (CD62E+) were unchanged (P > 0.05). PMVs were related to brachial artery shear rate (r2 = 0.43) and plasma norepinephrine concentrations (r2 = 0.21) during exercise (P < 0.05). Exercise-derived microvesicles enhanced endothelial proliferation, migration, and tubule formation compared with rest microvesicles (P < 0.05). These results demonstrate substantial increases in circulating PMVs during heavy exercise and that exercise-derived microvesicles stimulate human endothelial cells by enhancing angiogenesis and proliferation. This involvement of microvesicles may be considered a novel mechanism through which exercise mediates vascular healing and adaptation.

Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans.

Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in flow-mediated dilatation (FMD). Ten healthy male subjects (28 ± 5 years) undertook two 30 min sessions of cycle exercise at 75% HR(max). Prior to exercise, individuals ingested either a placebo or an α1-adrenoreceptor blocker (prazosin; 0.05 mg kg(-1)). Central haemodynamics, brachial artery shear rate (SR) and blood flow profiles were assessed throughout each exercise bout and in response to brachial artery FMD, measured prior to, immediately after and 60 min after exercise. Cycle exercise increased both mean and antegrade SR (P < 0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre-exercise FMD was similar on both occasions, and was significantly reduced (27%) immediately following exercise in the placebo condition (t-test, P = 0.03). In contrast, FMD increased (37%) immediately following exercise in the prazosin condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD remained different between conditions after correction for baseline diameters preceding cuff deflation and also post-deflation SR. No differences in FMD or other variables were evident 60 min following recovery. Our results indicate that sympathetic vasoconstriction competes with endothelium-dependent dilator activity to determine post-exercise arterial function. These findings have implications for understanding the chronic impacts of interventions, such as exercise training, which affect both sympathetic activity and arterial shear stress.

Opposing effects of shear-mediated dilation and myogenic constriction on artery diameter in response to handgrip exercise in humans.

While the impact of changes in blood flow and shear stress on artery function are well documented, the acute effects of increases in arterial pressure are less well described in humans. The aim of this study was to assess the effect of 30 min of elevated blood pressure, in the absence of changes in shear stress or sympathetic nervous system (SNS) activation, on conduit artery diameter. Ten healthy male subjects undertook three sessions of 30 min unilateral handgrip exercise at 5, 10, and 15% of maximal voluntary contractile (MVC) strength. Brachial artery shear rate and blood flow profiles were measured simultaneously during exercise in the active and contralateral resting arms. Bilateral brachial artery diameter was simultaneously assessed before and immediately postexercise. In a second experiment, six subjects repeated the 15% MVC condition while continuous vascular measurements were collected during muscle sympathetic nerve activity (MSNA) assessment using peroneal microneurography. We found that unilateral handgrip exercise at 5, 10, and 15% MVC strength induced stepwise elevations in blood pressure (P < 0.01, Δmean arterial pressure: 7.06 ± 2.44, 8.50 ± 2.80, and 18.35 ± 3.52 mmHg, P < 0.01). Whereas stepwise increases were evident in shear rate in the exercising arm (P < 0.001), no changes were apparent in the nonexercising limb (P = 0.42). Brachial artery diameter increased in the exercising arm (P = 0.02), but significantly decreased in the nonexercising arm (P = 0.03). At 15% MVC, changes in diameter were significantly different between arms (interaction effect: P = 0.01), whereas this level of exertion produced no significant changes in MSNA. We conclude that acute increases in transmural pressure, independent of shear rate and changes in SNS activation, reduce arterial caliber in normotensive humans in vivo. These changes in diameter were mitigated by exercise-induced elevations in shear rate in the active limb.

Resting brachial artery shear rate is associated with exercise habituation in middle aged and older adults

Hemodynamic shear stress, a frictional force of blood on the arterial wall, decreases with aging. The reduction in shear stress involved in development and progression of vascular endothelial dysfunction, a risk factor of cardiovascular disease. Habitual exercise is an effective strategy to improve vascular endothelial function. However, the effect of habitual exercise on the resting shear stress is unknown. The aim of this study was to determine whether brachial artery shear stress correlates with exercise habituation in middle aged and older adults.A total of 112 healthy middle aged and older adults (50–76 years) participated in this study. We measured peak and mean brachial artery shear rates, as indices of shear stress, at rest. Daily step counts and maximum oxygen consumption (VO2max) were measured as an index of exercise habituation. Subjects were divided into the inactive group (&lt; 7500 steps/day) and the active group (蠅 7500 steps/day).VO2max was significantly higher in the active group than in the inactive group (P &lt; 0.01). Peak shear rate and mean shear rate in the active group were significantly higher than in the inactive group (P &lt; 0.01 and P &lt; 0.05). VO2max correlated significantly with peak (r = 0.362, P &lt; 0.01) and mean shear rates (r = 0.302, P &lt; 0.05). These associations were remained significant even when adjusted for age.These results suggest that habitual exercise may increase resting brachial artery shear stress in middle‐aged and older adults.

Abstract P190: The Associations of Brachial Artery Shear Rate and Endothelial Dysfunction with Age Related Carotid Distensibility

Loss of carotid artery distensibility (CD) with age portends of clinical cerebrovascular disease. Endothelial dysfunction mediated by impaired nitric oxide vascular dilatation precedes vascular remodeling and age-related stiffening of arteries. However, it is unknown whether endothelial dysfunction contributes to loss of vascular distensibility with age. Methods: We examined 828 asymptomatic healthy subjects in the GeneSTAR family cohort, identified from index cases with early-onset coronary artery disease. We determined mean CD of both common carotid arteries using ultrasound; CD was quantified as the pulsatile change in lumen diameter/diastolic lumen diameter/brachial pulse pressure. Vascular shear rate (SR) was determined in the brachial artery as 4 х maximum blood flow velocity/maximum lumen diameter, and brachial flow mediated dilatation (FMD), a measure of endothelial dysfunction, as % change in diastolic diameter during reactive hyperemia. We tabulated both rest and hyperemic responses by age, sex and race-indexed tertiles of CD generated by quantile regression. Generalized estimating equations (GEE) were used to estimate the family correlation corrected associations of CD with FMD and SR. Results: The sample was 60% female, 40% African American, with mean age 52 (SD 12) years. While SR was significantly associated with higher tertiles of CD, FMD was not (Table). Adjusted for age, sex and race, every 540/s (1 SD) higher of shear rate was significantly associated with a 6.2% higher CD (p = 0.019) but FMD was not associated at all (p = 0.54). This pattern remained after adjustment for LDL and HDL- cholesterol, hypertension, diabetes and smoking (p = 0.03 and 0.95, respectively). Conclusion: Higher vascular shear rate is associated with preserved arterial distensibility indexed for age. FMD is not related to CD. The pathophysiological interpretations of this finding need further study before either CD or vascular shear rate can be used for assessing stoke risk in a population at increased risk for vascular disease.

Retrograde shear rate in formerly preeclamptic and healthy women before and after exercise training: relationship with endothelial function

Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this relationship is altered by exercise training. Formerly PE women (32 ± 4 yr, n = 20) and controls (32 ± 4 yr, n = 20), all 6-12 mo postpartum, performed 12-wk aerobic exercise training. We measured brachial artery shear rate (SR) and endothelial function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed power spectral analysis of heart rate variability and calculated low-frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between groups, while retrograde SR was significantly higher and FMD% lower in PE women compared with controls (both P < 0.05). Retrograde shear correlated strongly with FMD% in PE women and controls (P < 0.05). LF/HF ratio inversely correlated with brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls. Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF ratios similarly in both groups (all P < 0.05). Training-induced changes in retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial artery retrograde SR relates to lower brachial artery endothelial function, in both controls and formerly PE women. Exercise training improves retrograde SR, while the magnitude of this change correlated strongly with improvements in FMD and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training on endothelial health may, at least partly, be related to retrograde shear rate.

Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate

Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P < 0.05 vs. baseline), whereas exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P < 0.05 vs. baseline). In conclusion, exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

Repeated core temperature elevation induces conduit artery adaptation in humans

Shear stress is a known stimulus to vascular adaptation in humans. However, it is not known whether thermoregulatory reflex increases in blood flow and shear can induce conduit artery adaptation. Ten healthy young volunteers therefore underwent 8 weeks of 3 × weekly bouts of 30 min lower limb heating (40 °C) during which the upper body was not directly heated. Throughout each leg heating session, a pneumatic cuff was placed on one forearm and inflated to unilaterally restrict reflex-mediated blood flow responses. Each bout of leg heating significantly increased brachial artery shear rate in the uncuffed arm (96 ± 97 vs 401 ± 96 l/s, P < 0.01), whereas no change was apparent in the cuffed arm (83 ± 69 vs 131 ± 76 l/s, P = 0.67). Repeated episodic exposure to leg heating enhanced brachial artery endothelial function (measured by flow-mediated dilation) in the uncuffed arm from week 0 (5.2 ± 1.9 %) to week 4 (7.7 ± 2.6 %, P < 0.05), before returning to baseline levels by week 8. No adaptation was evident in the cuffed arm. We conclude that repeated increases in core temperature, induced via lower limb heating, resulted in upper limb conduit artery vascular adaptation which was dependent upon increases in shear stress. To our knowledge this is the first study to establish a beneficial systemic impact of thermoregulatory reflexes on conduit artery function in humans.