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 μg/min) in unanesthetized, nonpregnant sheep both before and after treatment with either high-dose or low-dose 17β-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 < 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 · hr to 2.57 ± 0.39 and 3.21 ± 0.61 ng/ml · hr with low-dose and high-dose E₂, respectively (p < 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.