Effects of ETA- and ETB-receptor antagonists on regional kidney blood flow, and responses to intravenous endothelin-1, in anaesthetized rabbits

Objective To determine the roles of endothelin (ET)receptor subtypes in the effects of exogenous and endogenous ETs on regional kidney blood flow in a naesthetized rabbits. Design and methods The effects on regional kidney blood flow of the ETA ant agonist BQ610, and the ETB antagonist BQ788, were tested. We also examined the effects of intravenous and renal arterial bolus doses of ET-1, and how these responses are modified by pretreatment with BQ610 and BQ788. Results BO610 reduced mean arterial pressure (MAP, 3%), and increased total renal blood flow (RBF, 10%), cortical perfusion (CBF, 11%) and medullary p erfusion (MBF, 16%). BQ788 increased MAP (6%) and reduced RBF (16%) and CBF (13%) but not MBF. The effects of BQ788 were abolished by pretreatment wit h BQ610. Intravenous ET-1 (300 ng/kg) reduced RBF and CBF, but increased MB F. BQ788 potentiated ET-1 mediated reductions in CBF, and abolished increas es in MBF. BQ610 blunted reductions in RBF and CBF produced by ET-1, but di d not significantly affect MBF responses. The renal vascular effects of int ravenous ET-1 were mimicked by lower doses (1 - ng/kg) administered into th e renal artery. Conclusions Endogenous ETs act at ETA-receptors to reduce MBF and CBF, but ETB-receptors have little direct role in physiological control of renal hae modynamics. Bolus doses of ET-1 act at ETB-receptors in the kidney to incre ase MBF. The effects of bolus ET-1 on the cortical vasculature appear to re sult from the competing influences of ETA-mediated vasoconstriction and ETB -mediated vasodilatation. (C) 2001 Lippincott Williams & Wilkins.