Involvement of endothelin in renal processes.

Abstract

This study examined the effect of various doses of endothelin (from 0.2 to 2 nmol/kg body wt) on regional hemodynamics in conscious unrestrained rats. Normal rats were instrumented chronically with femoral artery and vein catheters and pulsed Doppler flow probes simultaneously on the renal and superior mesenteric arteries and the abdominal aorta. Endothelin induced a biphasic response of mean arterial pressure. First, endothelin provoked a sharp hypotension with tachycardia, vasodilation of the hindquarter, and a pronounced decrease in renal and mesenteric blood flows. After this initial response, endothelin induced a dose-dependent increase of mean arterial pressure. Changes in the hindquarter vascular resistance were less pronounced than those in renal and mesenteric vascular resistances. Endothelin (2 nmol/kg) reduced renal flow (-86%) resulting from a vasoconstriction (+1,818%) significantly more pronounced than for the mesenteric vascular bed. In another set of experiments, endothelin (2 nmol/kg) induced an increase in proteinuria, characterized by an increase in excreted albumin and by the appearance of proteins with molecular weights of 20,000-280,000. Renal vascular bed exhibited a pronounced sensitivity to the vasoconstrictive effect of endothelin associated with changes in renal function.