Evidence of sex differences in the acute impact of oscillatory shear stress on endothelial function

Abstract

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.

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

“…This is in contrast with previous reports suggesting that female conduit arteries may be protected against proatherogenic perturbations in shear stress (52). For instance, Tremblay et al (50) observed a reduction in FMD stimulated by a sustained increase in shear stress in men, but not women, after a similar 30-min forearm cuff intervention. Likewise, Vranish et al (52) observed preserved popliteal artery reactive hyperemia-induced FMD in women after 3 h of uninterrupted sitting (isolated low mean shear stress) compared with a consistent, considerable reduction in men.…”

“…Furthermore, this reduction was evident in both men and women. A previous study from our laboratory identified a decrease in reactive hyperemia-stimulated FMD in women following the forearm cuff intervention; however, there was a concomitant reduction in SR AUC such that covariate-correcting for the shear stress stimulus abolished the reduction in FMD (50). Through implementation of a longer duration of supine rest before preintervention measures (45 min versus 30 min), we were able to mitigate changes in the shear stress stimulus from before to after intervention.…”

Aerobic training and vascular protection: Insight from altered blood flow patterns

“…Although often unreported (Schreuder et al., , b), shear AUC, the stimulus for the FMD response, is commonly revealed to be unchanged (Thijssen et al., , ) afer 30 min of SDCI. However, two recent studies by Tremblay and colleagues corroborate the findings of the present study by identifying a significant reduction in shear AUC after a 30 min SDCI intervention (Tremblay, Howe, Ainslie, & Pyke, , ), implicating a change in the stimulus (shear AUC), not the response (BA FMD) after the SDCI intervention.…”

“…Another interesting finding in the present study was that, independent of group, the conduit arteries did not display any alterations in vascular function associated with acute increases in retrograde flow. This has been reported previously in only one study using the SDCI technique (Tremblay, Stimpson, & Pyke, ), but similar findings have been revealed in the lower limb conduit arteries after 1 h of reduced anterograde flow (Vranish et al., ) and in bed‐rest studies that reported similar or improved BA FMD measurements after 5–7 days of physical inactivity (Bonnin et al., ; Hamburg et al., ). Taken together, this might highlight a potential resiliency of conduit artery function in response to this specific type (increased retrograde/oscillatory shear) and magnitude (60 mmHg) of altered shear patterns.…”

“…Specific to the SDCI intervention, the present study did not release the SDCI before the onset of the second FMD, and instead obtained baseline measures for the second FMD while the SDCI was still at 60 mmHg. This is in contrast to prior studies that released the SDCI and completed the second FMD test immediately afterwards (Johnson, Mather, Newcomer, Mickleborough, & Wallace, , Tremblay et al., , ). Although the study findings mirrored the work of Tremblay and colleagues and was strengthened by the findings of the time control session, future research is needed to identify whether discrepancies in FMD assessment post‐SDCI exist when using these different techniques.…”