Vascular Responses to Angiotensin-(1-7) During the Estrous Cycle

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Abstract

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 (10−10–10–5M) were determined in arteries preconstricted with endothelin-1 (10−7M). Mesenteric arteries were pretreated with the specific Ang-(1-7) antagonist, D-[Ala7]-Ang-(1-7) (10−7M) 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 10−8M concentrations. Ang-(1-7) caused a concentration-dependent vasodilation in mesenteric arteries of females with E2 replacement, with an EC50 of 21 n MD -[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.

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