Myocardial and vascular actions of amiloride in spontaneously hypertensive rats

RJ Barrett and ST Kau

Experiments were conducted to characterize the cardiovascular actions of the potassium-sparing diuretic amiloride in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Amiloride produced dose-dependent and sustained reductions in blood pressure in spontaneously hypertensive, but not Wistar-Kyoto rats. In intact spontaneously hypertensive rats, amiloride reduced blood pressure, heart rate and myocardial oxygen consumption, and increased simultaneously myocardial contractility. The antihypertensive response was unaltered by bilateral nephrectomy, atropine, cimetidine plus mepyramine, sulpiride and ouabain, but was prevented by phentolamine, hexamethonium and reserpine. Pressor responses to norepinephrine, tyramine, phenylephrine and clonidine were depressed significantly after amiloride, suggesting that amiloride interfered with alpha adrenoceptor-mediated vasoconstriction; vascular reactivity to arginine vasopressin, isoproterenol, histamine and acetylcholine was unaltered. The bradycardic response to amiloride persisted in all groups of animals in spite of surgical or pharmacological pretreatments; positive chronotropic responses to isoproterenol were unaltered by amiloride. The positive inotropic responses to amiloride were evident in the presence of bradycardia, and under conditions in which afterload remained constant or was allowed to decrease. The negative chronotropic and positive inotropic actions of amiloride were due to a direct action of the drug on myocardial tissues, and occurred independently of the antihypertensive effect.

Volume 239, Issue 2, pp. 365-374, 11/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics