ET-receptor subtypes: Roles in regional renal vascular actions of exogenous and endogenous endothelins in anesthetized rabbits

The roles of endothelin (ET)-receptor subtypes, in the regional renal vascu lar effects of exogenous and endogenous ETs, were examined in pentobarbiton e-anesthetized rabbits. The effects of renal arterial infusion of ET-I (0.0 5-12.8 ng/kg/min) and the ETB-agonist [Ala(1,3,11,15)]-ET-1 (12.5-800 ng/kg /min) were compared. We then tested the effects of the ETA-antagonist BQ610 and the ETB-antagonist BQ788 (both 200 mu g/kg plus 100 mu g/kg/h, i.v.) o n basal hemodynamics and on responses to renal arterial ET-I. Both ET-I and [Ala(1,3,11,15)]-ET-1 dose-dependently reduced total renal blood flow (RBF ) and cortical blood flow (CBF), but not medullary blood flow (MBF). ET-1 w as 34-fold more potent than [Ala(1,3,11,15)]-ET-1. BQ610 reduced mean arter ial pressure (MAP; 14%), and increased RBF (21%) and CBF (12%), but not MBF . BQ788 increased MAP (13%), and reduced RBF (29%) and CBF (15%) but not MB F. Coadministration of both agents increased RBF (18%) and CBF (9%), withou t significantly affecting MAP. Neither antagonist (alone or combined) signi ficantly affected responses to renal arterial ET-1. We conclude that the pr edominant renal vascular effects of exogenous and endogenous ETs an cortica l vasoconstriction, but not at vascular sites controlling MBF. ETA-receptor s contribute to the renal vasoconstrictor effects of endogenous ETs. ETB2-l ike receptors appear to contribute to the vasoconstrictor effects of [Ala(1 ,3,11,15)]-ET-1.