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

Br J Pharmacol. 1998 Jul;124(5):930-4. doi: 10.1038/sj.bjp.0701923.

Abstract

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 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 microg min(-1) for 60 min and subsequently 60 microg 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / pharmacology
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Male
  • Peptides, Cyclic / pharmacology*
  • Pulse
  • Receptor, Endothelin A
  • Renal Circulation / drug effects*
  • Renal Plasma Flow / drug effects

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Peptides, Cyclic
  • Receptor, Endothelin A
  • cyclo(Trp-Asp-Pro-Val-Leu)