DEMONSTRATION OF AN IN-VITRO DIRECT VASCULAR RELAXANT EFFECT OF DIURETICS IN THE PRESENCE OF PLASMA

Objective To determine whether diuretics have direct vascular actions and to compare the in vitro effects of a loop diuretic with thiazide a nd thiazide-like diuretics. Design A randomized, double-blind, vehicle -controlled design was used to avoid experimenter bias. Methods Concen tration-response curves to hydrochlorothiazide, chlorthalidone, indapa mide, and furosemide were tested on the following male Wistar rat vasc ular smooth muscle preparations: rat aortic rings, rat pulmonary arter y rings, and rat mesenteric portal vein. Results All four diuretics de monstrated no vasorelaxant action in Krebs solution. They all exhibite d vasorelaxant actions in aortic and pulmonary artery rings when plasm a was mixed with Krebs solution in a 50:50 ratio. The magnitude of the relaxation was greater in the aortic ring preparation. This direct va scular action was found to be concentration dependent and endothelium independent The order of potency of the vasorelaxant action of the diu retics was (from most to least) indapamide, hydrochlorothiazide, chlor thalidone, and furosemide on both aortic and pulmonary artery rings. C onclusion Diuretics possess direct vasorelaxant effects that are depen dent upon the presence of plasma; this action may contribute to their antihypertensive properties.