Systemic and renal effects of an ETA receptor subtype-specific antagonist in healthy subjects |
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Authors: | Leopold Schmetterer Susanne Dallinger Barbara Bobr Nicole Selenko Hans-Georg Eichler Michael Wolzt |
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Affiliation: | 1.Department of Clinical Pharmacology, Währinger Gürtel 18-20, A-1090, Vienna, Austria;2.Institute of Medical Physics, Währinger Gürtel 18-20, A-1090, Vienna, Austria |
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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%, 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).
- 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.
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Keywords: | Endothelins renal plasma flow glomerular filtration rate renal vascular disease endothelinA receptors |
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