Vascular responses to angiotensin-(1-7) during the estrous cycle

Mesenteric arteries (230-290 μm) were isolated from virgin female rats at diestrous and proestrous phases of the estrous cycle and from ovariectomized (OVX) rats with or without estrogen (E₂) replacement (17β-estradiol, 7.5 + 5 mg pellets, 21 d release). Arteries were mounted in a pressurized myograph system. Angiotensin-(1-7) [Ang-(1-7)] concentration-dependent responses (10^-10-10^-5 M) were determined in arteries preconstricted with endothelin-1 (10^-7 M). Mesenteric arteries were pretreated with the specific Ang-(1-7) antagonist, D-[Ala⁷]-Ang-(1-7) (10^-7 M) to assess the Ang-(1-7) receptor-mediated dilator effect. Ang-(1-7) did not dilate mesenteric arteries from virgin rats at diestrus and placebo-treated OVX female rats as compared to the time control; however, Ang-(1-7) elicited a modest dilation at proestrus as compared to diestrus, which reached statistical significance at 10^-8 M concentrations. Ang-(1-7) caused a concentration-dependent vasodilation in mesenteric arteries of females with E₂ replacement, with an EC ₅₀ of 21 nM. D-[Ala⁷]-Ang-(1-7) blocked the vasodilator effect of Ang-(1-7). Our results demonstrate that during proestrus Ang-(1-7) elicits modest vasodilation as compared to diestrus, but lacks vasodilatory properties in vessels from diestrous and ovariectomized rats. Estrogen replacement restores a significant dilator response to Ang-(1-7) in OVX rats that is mediated by a D-[Ala⁷]-Ang-(1-7) sensitive site.