Inhibition of the slow pressor effect of angiotensin II contributes to the antihypertensive effect of angiotensin-converting enzyme inhibitors in renovascular hypertension

MG Melaragno and GD Fink

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, USA.

The authors recently reported that renovascular hypertension (RVH) in rats is associated with enhanced responsiveness to the slow pressor effect of angiotensin II (AngII). It was concluded that the contribution of AngII to the development of hypertension could not be inferred solely from measurements of plasma peptide concentrations. This experiment was performed to test the corollary hypothesis that the antihypertensive efficacy of angiotensin-converting enzyme inhibitors in established RVH could be caused in part by inhibition of the slow pressor effect. After five control days of measurement of mean arterial pressure (MAP) and other variables, RVH rats were given the angiotensin- converting enzyme inhibitor enalapril in their drinking water. Half of these rats also received a continuous infusion of AngII, 4 ng/min i.v., an infusion rate previously shown to restore normal MAP in normal rats rendered hypotensive by chronic treatment with enalapril. Other RVH rats were given the potent vasodilator minoxidil in their drinking water, and half of these received AngII. Treatments lasted 7 days and were followed by 5 days without intervention. Enalapril significantly reduced MAP, but concurrent AngII infusion overcame this effect; MAP remained at control hypertensive levels. AngII did not affect the antihypertensive response to minoxidil. These results confirm that addition of relatively modest amounts of AngII to the circulation is able to maintain elevated blood pressure in RVH. Thus, inhibition of the slow pressor effect of AngII may partially explain the antihypertensive effect of angiotensin-converting enzyme inhibitors in RVH.

Volume 278, Issue 1, pp. 297-303, 07/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

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