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Comparison of selective ET A and ET B receptor antagonists in patients with chronic heart failure
Author(s) -
Cowburn Peter J.,
Cleland John G.F.,
McDonagh Theresa A.,
McArthur John D.,
Dargie Henry J.,
Morton James J.
Publication year - 2005
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2004.08.001
Subject(s) - vasodilation , heart failure , endothelin receptor , medicine , vasoconstriction , receptor , endothelin 1 , endocrinology , receptor antagonist , hemodynamics , antagonist , hypoxic pulmonary vasoconstriction , pharmacology
Abstract Background The vasoconstrictor action of endothelin‐1 (ET‐1) is mediated through ET A and ET B receptor subtypes on vascular smooth muscle. ET B receptors are also present on the vascular endothelium where they mediate vasodilation. Animal studies suggest that the ET B receptor also acts as a clearance receptor for endothelin. Aims To investigate the effects of a selective ET A and a selective ET B receptor antagonist alone and in combination on haemodynamics and circulating concentrations of ET‐1 in patients with chronic heart failure. Results Infusion of BQ‐123 ( n =10), a selective ET A receptor antagonist, led to systemic vasodilation and did not change plasma ET‐1 concentrations (1.38±0.82 to 1.38±0.91 fmol/ml, ns). Infusion of BQ‐788 ( n =8) led to systemic vasoconstriction with a rise in plasma ET‐1 (1.84±1.06 to 2.73±0.99 fmol/ml, p <0.01). The addition of BQ‐123 to BQ‐788 led to systemic and pulmonary vasodilation with no further increase in plasma ET‐1 concentrations (2.80±1.14 to 2.90±1.20 fmol/ml, ns). Conclusion The rise in plasma ET‐1 concentrations in response to selective blockade of ET B receptors and the associated adverse haemodynamic effects suggest that ET B receptors have a role in the clearance of ET‐1 in man and that their blockade may not be advantageous for patients with heart failure.