Paradoxical Role of Angiotensin Ii Type 2 Receptors in Resistance Arteries of Old Rats

The role of angiotensin II type 2 receptors (AT2R) remains a matter of controversy. Its vasodilatory and antitrophic properties are well accepted. Nevertheless, in hypertensive rats AT2R stimulation induces a vasoconstriction counteracting flow‐mediated dilation (FMD). This contraction is reversed by hydralazine. As FMD is decreased in aging, we determined the involvement of AT2R in FMD in old rats resistance arteries. Mesenteric resistance arteries (250 μm diameter) were isolated from old (24 months) and control (4 months) rats receiving hydralazine (16 mg/kg/day, 2 weeks) or water. FMD, NO‐mediated dilation and eNOS expression were lower in old than in control rats. AT2R blockade improved FMD in old rats, suggesting that AT2R stimulation produced vasoconstriction. AT2R expression was higher in old rats and mainly located in the smooth muscle layer. In old rats AT2R stimulation induced endothelium‐independent contraction, which was suppressed by the antioxydant Tempol. Reactive oxygen species (ROS) level was higher in old rats arteries than in controls. Hydralazine improved FMD and NO‐dependent dilation in old rats without change in AT2R expression and location. In old rats treated with hydralazine ROS level was reduced in endothelial and smooth muscle cells and AT2R‐dependent contraction was abolished. AT2R stimulation induced vasoconstriction through activation of ROS production, contributing to decrease FMD in old rats resistance arteries. Hydralazine suppressed AT2R‐dependent ROS production and AT2R‐dependent contraction, improving FMD. Endothelial alterations in aging were reversible which is important in the choice of vasoactive drugs in aging.