Estrogen-induced refractoriness to the pressor effects of infused angiotensin II

Estrogen may be important in the hemodynamic changes that develop during pregnancy; its role in the development of vascular refractoriness to the pressor effects of infused angiotensin II is unknown. We, therefore, examined the pressor responses to six doses of angiotensin II (0.115 to 5.73 micrograms/min) in unanesthetized, nonpregnant sheep both before and after treatment with either high-dose or low-dose 17 beta-estradiol (E2) and constructed dose-response curves. Although mean arterial pressure was unchanged after the infusion of E2, cardiac output rose 28% and systemic vascular resistance fell 19% (p less than 0.001). Infused angiotensin II resulted in dose-dependent rises in mean arterial pressure before and after E2; however, the pressor response after E2 was decreased 30% to 50%. Plasma renin activity rose from 1.15 +/- 0.09 ng/ml X hr to 2.57 +/- 0.39 and 3.21 +/- 0.61 ng/ml X hr with low-dose and high-dose E2, respectively (p less than 0.05). Acutely estrogenized nonpregnant sheep develop significant alterations in both the cardiovascular and the renin-angiotensin systems in addition to decreased pressor responsiveness to infused angiotensin II. Although our findings suggest that estrogen may be important in the development of the vascular refractoriness to angiotensin II seen in pregnancy, additional studies are needed to clarify the role of each E2-induced change.