Systemic ETA receptor antagonism with BQ-123 blocks ET-1 induced forearm vasoconstriction and decreases peripheral vascular resistance in healthy men

Br J Pharmacol. 2001 Oct;134(3):648-54. doi: 10.1038/sj.bjp.0704304.


1. The effect on systemic haemodynamics of BQ-123, a selective endothelin A (ETA) receptor antagonist, was investigated in healthy men by giving, on separate occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min(-1) BQ-123, each for 15 min, in a randomized, placebo-controlled, double-blind study. The response of forearm blood flow to brachial artery infusion of endothelin-1 (ET-1; 5 pmol min(-1) for 90 min) was also studied using bilateral forearm plethysmography, after systemic pre-treatment, on separate occasions, with one of two doses of BQ-123 (300 and 1000 nmol min(-1) for 15 min) or placebo. 2. Systemic BQ-123 dose-dependently decreased systemic vascular resistance (P<0.01 for all doses vs placebo) and mean arterial pressure (P<0.05 for 300 nmol min(-1) and P<0.01 for 1000 and 3000 nmol min(-1)) during the 60 min following infusion. There were concurrent increases in heart rate and cardiac index. BQ-123, when infused systemically for 15 min, appeared to reach a maximum effect at 1000 nmol min(-1). 3. Intra-brachial ET-1 infusion, after pre-treatment with placebo, caused a slow onset progressive forearm vasoconstriction without systemic effects. This vasoconstriction was attenuated by pre-treatment with BQ-123 at 300 nmol min(-1) and abolished by BQ-123 at 1000 nmol min(-1) (P<0.01 vs placebo). 4. These effects occurred at concentrations of BQ-123 in the plasma (510+/-64 nmol l(-1)) that were ETA receptor selective, and were not accompanied by an increase in plasma ET-1 that would have indicated ETB receptor blockade. 5. We conclude that ETA-mediated vascular tone contributes to the maintenance of basal systemic vascular resistance and blood pressure in healthy men.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Antihypertensive Agents / pharmacology*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / pharmacology*
  • Forearm / physiology
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Male
  • Peptides, Cyclic / pharmacology*
  • Receptor, Endothelin A
  • Receptors, Endothelin / physiology
  • Vascular Resistance / drug effects*
  • Vascular Resistance / physiology
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology


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