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 and thiazide-like diuretics. Design A randomized, double-blind, vehicle-controlled design was used to avoid experimenter bias. Methods Concentration-response curves to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide were tested on the following male Wistar rat vascular smooth muscle preparations: rat aortic rings, rat pulmonary artery rings, and rat mesenteric portal vein. Results All four diuretics demonstrated no vasorelaxant action in Krebs solution. They all exhibited vasorelaxant actions in aortic and pulmonary artery rings when plasma was mixed with Krebs solution in a 50:50 ratio. The magnitude of the relaxation was greater in the aortic ring preparation. This direct vascular action was found to be concentration dependent and endothelium independent The order of potency of the vasorelaxant action of the diuretics was (from most to least) indapamide, hydrochlorothiazide, chlorthalidone, and furosemide on both aortic and pulmonary artery rings. Conclusion Diuretics possess direct vasorelaxant effects that are dependent upon the presence of plasma; this action may contribute to their antihypertensive properties.