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Heart. Jul 2005; 91(7): 914–919.
PMCID: PMC1768985
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, and D J Webb
Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Edinburgh, UK
Correspondence to:
Dr David J Webb
Clinical Pharmacology Unit & Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; d.j.webb/at/ed.ac.uk
Accepted August 18, 2004.
Abstract
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.
Keywords: endothelin, haemodynamic function, heart failure, receptors
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