Activation of AT(2) receptors by endogenous angiotensin II is involved in flow-induced dilation in rat resistance arteries

Pressure-induced tone (myogenic, MT) and flow (shear stress)-induced dilati on (FD) are potent modulators of resistance artery tone. We tested the hypo thesis that locally produced angiotensin II interacts with MT and FD, Rat m esenteric resistance arteries were perfused in situ. Arterial diameter was measured by intravital microscopy after a bifurcation on 2 distal arterial branches equivalent in size (150 mu m, n=7 per group). One was ligated dist ally and thus submitted to pressure only (MT, no FD). The second branch was submitted to flow and pressure (MT and FD). The difference in diameter bet ween the 2 vessels was considered to be FD. Flow-diameter-pressure relation ship was established in the absence and then in the presence of 1 of the. f ollowing agents. In the nonligated segment (MT+FD), angiotensin-II type 1 ( AT(1)) receptor blockade (losartan) had no significant effect, whereas angi otensin II type 2 (AT(2)) receptor blockade (PD123319) or saralasin (AT(1)AT(2) blocker) decreased the diameter significantly, by 9+/-1 and 10+/-0.8 mu m, respectively. Angiotensin II in the presence of losartan increased th e diameter by 18+/-0.6 mu m (inhibited by PD 123319). PD123319 or saralasin had no effect after NO:synthesis blockade or after endothelial disruption. In the arterial segment ligated distally (MT only), AT(1) or AT(2) recepto r blockade had no significant effect. AT(2)-dependent dilation represented 20% to 39% of FD (shear stress from 22 to 37 dyn/cm(2)), and AT(2)-receptor mRNA was found in mesenteric resistance arteries. Thus, resistance arteria l tone was modulated in situ by locally produced angiotensin II, which-migh t participate in flow-induced dilation through endothelial AT(2) receptor a ctivation of NO release.