Flow-mediated dilation stimulated by sustained increases in shear stress: a useful tool for assessing endothelial function in humans?

Investigations of human conduit artery endothelial function via flow-mediated vasodilation (FMD) have largely been restricted to the reactive hyperemia (RH) technique, wherein a transient increase in shear stress after the release of limb occlusion stimulates upstream conduit artery vasodilation (RH-FMD). FMD can also be assessed in response to sustained increases in shear stress [sustained stimulus (SS)-FMD], most often created with limb heating or exercise. Exercise in particular creates a physiologically relevant stimulus because shear stress increases, and FMD occurs, during typical day-to-day activity. Several studies have identified that various conditions and acute interventions have a disparate impact on RH-FMD versus SS-FMD, sometimes with only the latter demonstrating impairment. Indeed, evidence suggests that transient (RH) and sustained (SS) shear stress stimuli may be transduced via different signaling pathways, and, as such, SS-FMD and RH-FMD appear to offer unique insights regarding endothelial function. The present review describes the techniques used to assess SS-FMD and summarizes the evidence regarding 1) SS-FMD as an index of endothelial function in humans, highlighting comparisons with RH-FMD, and 2) potential differences in shear stress transduction and vasodilator production stimulated by transient versus sustained shear stress stimuli. The evidence suggests that SS-FMD is a useful tool to assess endothelial function and that further research is required to characterize the mechanisms involved and its association with long-term cardiovascular outcomes. NEW & NOTEWORTHY Sustained increases in peripheral conduit artery shear stress, created via distal skin heating or exercise, provide a physiologically relevant stimulus for flow-mediated dilation (FMD). Sustained stimulus FMD and FMD stimulated by transient, reactive hyperemia-induced increases in shear stress provide distinct assessments of conduit artery endothelial function.