[Endothelin receptor antagonists in heart failure]

Endothelin 1 is a vasoconstrictor and pro-hypertrophic peptide released by the endothelium, whose secretion increases in cardiac insufficiency in proportion to the haemodynamic alteration, notably the systolic pulmonary arterial pressure. It acts by binding to 2 receptors: receptor A, responsible for the vasoconstriction effect, and receptor B, which produces vasodilatation and permits the pulmonary clearance of the molecule present in the plasma. Blocking receptor A appears logical in view of the hormonal hypothesis which prevails in the pathophysiology of cardiac insufficiency, but the significance of blocking receptor B is under discussion. The immediate effect of receptor antagonists is vasodilatation, permitting a haemodynamic improvement in patients, but the benefit on dyspnoea or the evolution of the disease has not been established. Animal models show a beneficial effect of endothelin receptor antagonists on survival, which has not been confirmed by the first studies in humans. The latter are difficult to interpret: the increase in dosage should probably to be very progressive, the optimal dosage is difficult to determine and could be lower than the doses tested. Only the result of studies underway will indicate the place of these drugs in the therapeutic arsenal for cardiac insufficiency.