The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and vasopressin vs. norepinephrine in rats.

Abstract

To study the influence of acute and chronic angiotensin-converting enzyme blockade on the pressor response to exogenous angiotensin II, vasopressin and norepinephrine, we gave normal female Wistar rats 100 mg of captopril or 1 ml of 5% glucose twice daily by gavage for 2 weeks. On the 15th day, rats were anesthetized with pentobarbital, and dose-response curves to angiotensin II, lysine-vasopressin, and norepinephrine were obtained before and after intraperitoneal injection of 100 mg/kg of captopril or 1 ml of 5% glucose. Acute as well as chronic converting enzyme blockade enhanced the pressor response to exogenous angiotensin II. Similarly, sensitivity to exogenous vasopressin was increased by both acute and chronic converting enzyme inhibition. In contrast, chronic converting enzyme blockade significantly blunted the response to exogenous norepinephrine, whereas acute blockade tended to accentuate its pressor effect. These results suggest that chronic angiotensin-converting enzyme blockade may partly inhibit sympathetic activity which, in turn, might contribute to the antihypertensive efficacy of this therapeutic approach. These results also point to an important physiological interaction between the two pressor hormones, angiotensin II and vasopressin.