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 dilation (FD) are potent modulators of resistance artery tone. We tested the hypothesis that locally produced angiotensin II interacts with MT and FD. Rat mesenteric 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 microm, n=7 per group). One was ligated distally 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 between the 2 vessels was considered to be FD. Flow-diameter-pressure relationship was established in the absence and then in the presence of 1 of the following agents. In the nonligated segment (MT+FD), angiotensin II type 1 (AT(1)) receptor blockade (losartan) had no significant effect, whereas angiotensin 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 microm, respectively. Angiotensin II in the presence of losartan increased the diameter by 18+/-0.6 microm (inhibited by PD123319). 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) receptor 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 arterial tone was modulated in situ by locally produced angiotensin II, which might participate in flow-induced dilation through endothelial AT(2) receptor activation of NO release.