Endothelium-dependent, shear-induced vasodilation is rate-sensitive

Objectives: To quantify the relative contributions of the rate of change an d the magnitude of shear stress to endothelium-mediated arteriolar dilation . Methods: A feedback control system a as designed in which shear stress (tau ) and the temporal shear gradient (TSG) were prescribed and dynamically con trolled in isolated rat cremaster 1A arterioles. The TSG was the quotient o f the maximum shear stress and the ramp duration. This system was used to a ssess the roles of tau and TSG in the initial, transient vasodilations and the secondary, sustained vasodilations in response to steps and ramps in sh ear stress. Results: Both step- and ramp-shear experiments revealed time-dependent biph asic vasodilations that we report for the first time. Application of a step -shear stress of 20 dynes/cm(2) elicited an initial transient vasodilation that peaked at about 4 min. When the shear stress was applied as a ramp tha t reached the maximum value of 20 dynes/cm(2) over 5 min, a vasodilation wa s observed over the ramp period, which reached a peak at the end of the ram p period that was much lower than that observed after step shear. After 20 dynes/cm(2) was attained, the vessel diameter decreased despite constant ma intenance of the maximum shear stress. In both step- and ramp-shear experim ents, after the decrease of the initial vasodilation, a second phase of vas odilation began approximately 15 min after the beginning of the shear appli cation. The second phase of vasodilation reached a steady state that a as e ssentially the same for both the step and the ramp shear. By refining the r amping apparatus further, we varied the TSG up to 40 dynes/cm(2) per second and showed that the early vasodilation was highly rate sensitive to TSGs g reater than 5 dynes/cm(2) per second for a given intermediate value of fina l shear stress (20 dynes/cm(2)) and was magnitude sensitive when shear gas increased gradually (TSG < 5 dynes/cm(2) per second). Conclusions: Our results suggest that two fundamentally different responses to shear stress are mediated by microvascular endothelium: one vasodilatio n is elicited by shear stress changes on a time scale of a few seconds or l ess and another is elicited by shear stress changes on a longer time scale. The former response is potent, transient, and rate sensitive: the latter i s more modest, sustained, and magnitude sensitive.