Impact of 2-Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men

Background Although acute elevation in retrograde shear rate (SR) impairs endothelial function, no previous study has explored the effect of prolonged elevation of retrograde SR on conduit artery vascular function. We examined the effect of 2‐weeks elevation of retrograde SR on brachial artery endothelial function in young and in older men. Methods and Results Thirteen healthy young (23±2 years) and 13 older men (61±5 years) were instructed to continuously wear a compression sleeve around the right forearm to chronically (2 weeks) elevate brachial artery retrograde SR in 1 arm. We assessed SR, diameter, and flow‐mediated dilation in both the sleeve and contralateral control arms at baseline and after 30 minutes and 2 weeks of continuous sleeve application. The sleeve intervention increased retrograde SR after 30 minutes and 2 weeks in both young and older men (P=0.03 and 0.001, respectively). In young men, brachial artery flow‐mediated dilation % was lower after 30 minutes and 2 weeks (P=0.004), while resting artery diameter was reduced after 2 weeks (P=0.005). The contralateral arm showed no change in retrograde SR or flow‐mediated dilation % (P=0.32 and 0.26, respectively), but a decrease in diameter (P=0.035). In older men, flow‐mediated dilation % and diameter did not change in either arm (all P>0.05). Conclusions Thirty‐minute elevation in retrograde SR in young men caused impaired endothelial function, while 2‐week exposure to elevated levels of retrograde SR was associated with a comparable decrease in endothelial function. Interestingly, these vascular changes were not present in older men, suggesting age‐related vascular changes to elevation in retrograde SR

Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial dysfunction in healthy subjects and those with type 2 diabetes

Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia- mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched T2DM patients underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow- mediated dilation (FMD), using high-resolution echo-Doppler. FMD was examined before and 60, 120 and 150 minutes after a 75-gr oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups (P<0.001). Forearm skin temperature, brachial artery BF and shear rate significantly increased in the heated arm (P<0.001), and to a greater extent compared to the non-heated arm in both groups (interaction- effect, P<0.001). The glucose load caused a transient decrease in FMD% (P<0.05), whilst heating significantly prevented the decline (interaction-effect: P<0.01). Also when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating (P<0.05). These effects on FMD were observed in both groups. Our data indicate that non-metabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions increasing BF and shear rate equally protect the endothelium when challenged by hyperglycemia

Cocoa-flavanols enhance moderate-intensity pulmonary [Formula: see text] kinetics but not exercise tolerance in sedentary middle-aged adults.

INTRODUCTION: Cocoa flavanols (CF) may exert health benefits through their potent vasodilatory effects, which are perpetuated by elevations in nitric oxide (NO) bioavailability. These vasodilatory effects may contribute to improved delivery of blood and oxygen (O2) to exercising muscle. PURPOSE: Therefore, the objective of this study was to examine how CF supplementation impacts pulmonary O2 uptake ([Formula: see text]) kinetics and exercise tolerance in sedentary middle-aged adults. METHODS: We employed a double-blind cross-over, placebo-controlled design whereby 17 participants (11 male, 6 female; mean ± SD, 45 ± 6 years) randomly received either 7 days of daily CF (400 mg) or placebo (PL) supplementation. On day 7, participants completed a series of 'step' moderate- and severe-intensity exercise tests for the determination of [Formula: see text] kinetics. RESULTS: During moderate-intensity exercise, the time constant of the phase II [Formula: see text] kinetics ([Formula: see text]) was decreased by 15% in CF as compared to PL (mean ± SD; PL 40 ± 12 s vs. CF 34 ± 9 s, P = 0.019), with no differences in the amplitude of [Formula: see text] (A[Formula: see text]; PL 0.77 ± 0.32 l min-1 vs. CF 0.79 ± 0.34 l min-1, P = 0.263). However, during severe-intensity exercise, [Formula: see text], the amplitude of the slow component ([Formula: see text]) and exercise tolerance (PL 435 ± 58 s vs. CF 424 ± 47 s, P = 0.480) were unchanged between conditions. CONCLUSION: Our data show that acute CF supplementation enhanced [Formula: see text] kinetics during moderate-, but not severe-intensity exercise in middle-aged participants. These novel effects of CFs, in this demographic, may contribute to improved tolerance of moderate-activity physical activities, which appear commonly present in daily life. TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT04370353, 30/04/20 retrospectively registered

Relationship Between Endothelial Function and the Eliciting Shear Stress Stimulus in Women: Changes Across the Lifespan Differ to Men.

Background Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate ( SR ) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow-mediated dilation [ FMD ]) and SR (ie, SR area under the curve [ SRAUC ]) in women versus men, and between pre- versus postmenopausal women. Methods and Results Brachial artery FMD and SRAUC were measured in accordance with expert-consensus guidelines in 932 healthy participants who were stratified into young adults (18-40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age-sex× SRAUC ) in linear regression revealed differential relationships with FMD (young women versus young men [β=-5.8-4, P=0.017] and older women [β=-5.9-4, P=0.049]). The correlation between SRAUC and FMD in premenopausal women ( r2=0.097) was not statistically different from that in postmenopausal women ( r2=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD - SRAUC correlation in young women compared with young men and older women. Conclusions Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes