ET-Receptor Subtypes: Roles in Regional Renal Vascular Actions of Exogenous and Endogenous Endothelins in Anesthetized Rabbits

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Abstract
The roles of endothelin (ET)-receptor subtypes, in the regional renal vascular effects of exogenous and endogenous ETs, were examined in pentobarbitone-anesthetized rabbits. The effects of renal arterial infusion of ET-1 (0.05-12.8 ng/kg/min) and the ETB-agonist [Ala1,3,11,15]-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 μg/kg plus 100 μg/kg/h, i.v.) on basal hemodynamics and on responses to renal arterial ET-1. Both ET-1 and [Ala1,3,11,15]-ET-1 dose-dependently reduced total renal blood flow (RBF) and cortical blood flow (CBF), but not medullary blood flow (MBF). ET-1 was 34-fold more potent than [Ala1,3,11,15]-ET-1. BQ610 reduced mean arterial 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 MBF. Coadministration of both agents increased RBF (18%) and CBF (9%), without significantly affecting MAP. Neither antagonist (alone or combined) significantly affected responses to renal arterial ET-1. We conclude that the predominant renal vascular effects of exogenous and endogenous ETs are cortical vasoconstriction, but not at vascular sites controlling MBF. ETA-receptors contribute to the renal vasoconstrictor effects of endogenous ETs. ETB2-like receptors appear to contribute to the vasoconstrictor effects of [Ala1,3,11,15]-ET-1.