Systemic and renal effects of an ET(A) receptor subtype-specific antagonist in healthy subjects

1. Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ET(A) receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1. 2. The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way crossover design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg^-1 min^-1 for 120 min) or placebo and BQ-123 (15 μg min^-1 for 60 min and subsequently 60 μg min^-1 for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively. 3. BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (-24%, P < 0.001) and GFR (-12%, P = 0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P = 0.0012; GFR: P = 0.020). 4. BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ET(A) receptor subtype.