Vascular responses to Angiotensin-(1-7) during the estrous cycle.
Mesenteric arteries (230-290 microm) 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 (17beta-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 EC50 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.
Neves
Liomar A A
LA
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
Averill
David B
DB
Ferrario
Carlos M
CM
Aschner
Judy L
JL
Brosnihan
K Bridget
KB
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004031:Diestrus; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects; D010052:Ovariectomy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010919:Placebos; D011359:Proestrus; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D019332:Endothelin-1; D010446:Peptide Fragments; D010919:Placebos; D004958:Estradiol; D000803:Angiotensin I; C118790:angiotensin I (1-7)