Modulation of angiotensin II pressor responsiveness by circulating levels of angiotensin II in pregnant sheep

Abstract

During human and ovine pregnancy, systemic pressor responses to infused angiotensin II are decreased when compared to the nonpregnant state. An increased circulating level of angiotensin II has been proposed as one of the possible mechanisms responsible for this refractoriness. The present study was designed to determine if increased pressor responsiveness to exogenous angiotensin II occurs after circulating levels of angiotensin II in pregnant ewes are reduced. Pregnant (112 to 118 days' gestation) and nonpregnant sheep were instrumented with catheters in the femoral artery and vein. Dose-response curves to angiotensin I, angiotensin II, and norepinephrine were established prior to and during continuous short-term (2 to 3 hours' duration) and long-term (24 hours' duration) inhibition of angiotensin converting enzyme activity by either captopril or enalapril. Short-term infusions of converting enzyme inhibitors blocked the formation of angiotensin II from exogenously administered angiotensin I but did not alter pressor responsiveness to angiotensin II or norepinephrine in pregnant and nonpregnant sheep. Long-term infusions of the angiotensin converting enzyme inhibitor enalapril blocked responses to angiotensin I but did not alter pressor responses to norepinephrine in pregnant and nonpregnant sheep. In contrast, responses to angiotensin II were significantly potentiated in pregnant sheep but were not altered in nonpregnant sheep. These results suggest that increased circulating levels of angiotensin II in pregnant sheep are responsible for pregnancy-induced decreases in angiotensin II responsiveness.