Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure

S J Leslie, J C S Spratt, S P McKee, F E Strachan, D E Newby, D B Northridge, M A Denvir, D J Webb

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)914-9
Number of pages6
JournalHeart
Volume91
Issue number7
DOIs
Publication statusPublished - 1 Jul 2005

Keywords / Materials (for Non-textual outputs)

  • Adult
  • Aged
  • Antihypertensive Agents
  • Cardiac Output
  • Cardiac Output, Low
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Endothelin-1
  • Female
  • Heart Rate
  • Hemodynamics
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • Treatment Outcome
  • Ventricular Function

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