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

Abstract

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.

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…; Tremblay et al . ), and thus, alterations in baseline shear stress magnitude and pattern may contribute to the observed reductions in endothelial function. To further investigate the effects of shear stress on endothelial function, two studies during the 2016 UBC‐Nepal Expedition (Willie et al .…”

“…Furthermore, OSS is enhanced with ageing (Casey et al 2012), pre-eclampsia (Scholten et al 2014), menopause (Somani et al 2019) and anabolic steroid use (de Souza et al 2019). To examine the causality of OSS it can be experimentally induced in otherwise healthy upstream arteries by inflating a pneumatic cuff on the forearm to a moderate pressure (ß50-75 mmHg; Thijssen et al 2009;Tremblay et al 2019a). Exposure to 20-30 min of low shear stress and/or OSS has been shown to reduce brachial artery endothelial function in healthy humans (Thijssen et al 2009;Tremblay et al 2019a).…”

“…To examine the causality of OSS it can be experimentally induced in otherwise healthy upstream arteries by inflating a pneumatic cuff on the forearm to a moderate pressure (ß50-75 mmHg; Thijssen et al 2009;Tremblay et al 2019a). Exposure to 20-30 min of low shear stress and/or OSS has been shown to reduce brachial artery endothelial function in healthy humans (Thijssen et al 2009;Tremblay et al 2019a). However, populations with pre-existing endothelial dysfunction (i.e.…”

“…Acute and sustained hypoxic exposure has been shown to increase retrograde shear stress (Iwamoto et al 2015;Katayama et al 2016;Lewis et al 2017;Tremblay et al 2018a,b), and decrease mean shear stress (Lewis et al 2017;Tremblay et al 2018a,b). These pro-atherogenic alterations in shear stress have a well-established deleterious impact on endothelial function (Padilla et al 2009;Thijssen et al 2009;Tremblay et al 2019a), and thus, alterations in baseline shear stress magnitude and pattern may contribute to the observed reductions in endothelial function. To further investigate the effects of shear stress on endothelial function, two studies during the 2016 UBC-Nepal Expedition (Willie et al 2018) examined endothelial function and performed measures of blood viscosity to calculate the shear stress stimulus during a 9-day trekking ascent to 5050 m, and following 5-7 days at 5050 m (Tremblay et al 2018a,b).…”

Endothelium function dependence of acute changes in pulse wave velocity and flow-mediated slowing

“…Endothelial function naturally fluctuates throughout the day and is enhanced or impaired by external and internal factors which alter the local hemodynamic environment. 2 , 19 – 23 For example, while unidirectional shear stress enhances endothelial function, 19 oscillatory shear stress can impair endothelial function. 19 – 22 A model that we 20 and others 21 , 22 have used to increase retrograde, and subsequently oscillatory shear stress, and acutely impair endothelial function, is the inflation of a tourniquet to a low-moderate pressure (50–75 mmHg) distal to the arterial segment of interest for 20-30 min.…”