SYSTEMIC AND RENAL EFFECTS OF AN ETA-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 ETA receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baselin e and during infusion of exogenous ET-1. 2 The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way crossov er 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 mu g min(-1) for 60 min and subsequently 60 mu g min(-1) for 60 min) o r placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR ) were assessed by the paraaminohippurate (PAH) and the inulin plasma clearance method, respectively. 3 BQ-123 alone had no renal or systemi c haemodynamic effect. ET-1 significantly reduced RPF (-24%, P<0.001) and GFR (-12%, P=0.034). These effects were abolished by co-infusion o f either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020). 4 BQ-123 revers ed the renal haemodynamic effects induced by exogenous ET-1 ill vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ETA receptor subtype.