Assessing limb conduit artery endothelial function with flow-mediated dilation in response to sustained, exercise-induced increases in shear stress.

Vascular endothelial function can be interrogated by imposing blood flow-associated shear stress, which stimulates endothelial-dependent dilation [flow-mediated dilation (FMD)]. A larger FMD response is indicative of better endothelial function. In the well-established technique used to assess human conduit artery endothelial function, a shear stress stimulus is created via the release of temporary limb occlusion, which results in a transient reactive hyperemia (RH; RH-FMD). However, sustained increases in shear stress created with small muscle mass exercise, limb heating or distal vasodilator infusion can also be used to stimulate conduit artery FMD to interrogate endothelial function [sustained stimulus FMD (SS-FMD)]. Cell and animal evidence suggests that endothelial shear stress transduction depends on the duration of the shear stress stimulus such that transient and sustained shear stress exposure recruit distinct signaling pathways. Furthermore, work in humans has demonstrated that RH-FMD and SS-FMD provide unique insight regarding the impact of interventions and clinical conditions on endothelial function. This suggests that testing both RH-FMD and SS-FMD may provide a more comprehensive picture of endothelial function; however, SS-FMD is rarely performed. Here, we describe how SS-FMD can be assessed in the brachial artery using handgrip exercise to achieve either a target shear stress stimulus or an incremental increase in shear stress stimulus.NEW & NOTEWORTHY This article provides the first methodological guide to utilize handgrip exercise for assessment of SS-FMD in the brachial artery in response to targeted steady state and incremental increases in shear stress. SS-FMD is a physiologically relevant response, reflecting conduit artery behavior during sustained exertional activity and can provide distinct information regarding endothelial function compared with reactive hyperemia-FMD.