Systemic and renal effects of an ETA receptor subtype‐specific antagonist in healthy subjects

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Abstract
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 ETA receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET‐1. The study was performed in a balanced, randomized, placebo‐controlled, double blind 4 way cross‐over 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. BQ‐123 alone had no renal or systemic haemodynamic effect. ET‐1 significantly reduced RPF (−24%, PP=0.034). These effects were abolished by co‐infusion of either dose of BQ‐123 (RPF: P=0.0012; GFR: P=0.020). 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 ETA receptor subtype.