Comparison of Selective ETA and ETB Receptor Antagonists in Patients with Chronic Heart Failure

Abstract

Abstract Background The vasoconstrictor action of endothelin-1 (ET-1) is mediated through ETA and ETB receptor subtypes on vascular smooth muscle. ETB receptors are also present on the vascular endothelium where they mediate vasodilation. Animal studies suggest that the ETB receptor also acts as a clearance receptor for endothelin. Aims To investigate the effects of a selective ETA and a selective ETB 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 ETA 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 ETB receptors and the associated adverse haemodynamic effects suggest that ETB 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.