Article Text

Download PDFPDF
Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure
  1. S J Leslie,
  2. J C S Spratt,
  3. S P McKee,
  4. F E Strachan,
  5. D E Newby,
  6. D B Northridge,
  7. M A Denvir,
  8. D J Webb
  1. Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Edinburgh, UK
  1. Correspondence to:
    Dr David J Webb
    Clinical Pharmacology Unit & Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK;


Objective: To investigate the potential differential effects of selective endothelin (ET) A and dual ET-A/B receptor blockade in patients with chronic heart failure.

Methods: Nine patients with chronic heart failure (New York Heart Association class II–III) each received intravenous infusions of BQ-123 alone (selective ET-A blockade) and combined BQ-123 and BQ-788 (dual ET-A/B blockade) in a randomised, placebo controlled, three way crossover study.

Results: Selective ET-A blockade increased cardiac output (maximum mean (SEM) 33 (12)%, p < 0.001) and reduced mean arterial pressure (maximum −13 (4)%, p < 0.001) and systemic vascular resistance (maximum −26 (8)%, p < 0.001), without changing heart rate (p  =  0.38). Dual ET-A/B blockade significantly reduced the changes in all these haemodynamic variables compared with selective ET-A blockade (p < 0.05). Selective ET-A blockade reduced pulmonary artery pressure (maximum 25 (7)%, p  =  0.01) and pulmonary vascular resistance (maximum 72 (39)%, p < 0.001). However, there was no difference between these effects and those seen with dual ET-A/B blockade. Unlike selective ET-A blockade, dual ET-A/B blockade increased plasma ET-1 concentrations (by 47 (4)% with low dose and 61 (8)% with high dose, both p < 0.05).

Conclusions: While there appeared to be similar reductions in pulmonary pressures with selective ET-A and dual ET-A/B blockade, selective ET-A blockade caused greater systemic vasodilatation and did not affect ET-1 clearance. In conclusion, there are significant haemodynamic differences between selective ET-A and dual ET-A/B blockade, which may determine responses in individual patients.

  • endothelin
  • haemodynamic function
  • heart failure
  • receptors

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Grant Support British Heart Foundation (PG/99043 and FS/98040)