Document Detail

Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure.
MedLine Citation:
PMID:  15958361     Owner:  NLM     Status:  MEDLINE    
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.
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
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  91     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-16     Completed Date:  2005-08-17     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  914-9     Citation Subset:  AIM; IM    
Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
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MeSH Terms
Antihypertensive Agents / administration & dosage*
Cardiac Output / physiology
Cardiac Output, Low / drug therapy*,  physiopathology
Cross-Over Studies
Drug Therapy, Combination
Endothelin-1 / blood
Heart Rate / physiology
Hemodynamics / physiology
Infusions, Intravenous
Middle Aged
Oligopeptides / administration & dosage*
Peptides, Cyclic / administration & dosage*
Piperidines / administration & dosage*
Receptor, Endothelin A / antagonists & inhibitors
Receptors, Endothelin / antagonists & inhibitors*
Treatment Outcome
Ventricular Function / physiology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Antihypertensive Agents; 0/BQ 788; 0/Endothelin-1; 0/Oligopeptides; 0/Peptides, Cyclic; 0/Piperidines; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu)

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