[Endothelin-1 receptor antagonists in heart failure]

Endothelin-1 is a vasoconstrictor peptide playing an important role in the pathophysiology of heart failure. Endothelin-1 acts after fixation to 2 specific receptors: type A, responsible for vasoconstriction and type B, at the start of transient vasodilation and participating in clearance of the hormone. The experimental results in various animal models have demonstrated beneficial haemodynamic and clinical effects of the mixed or specific antagonists of the type A receptor. The preliminary results of studies conducted in man have confirmed the beneficial haemodynamic effects with lowering of pulmonary pressures, lowering of vascular resistance, and increase in cardiac output. On the other hand, the results of clinical studies have been disappointing, with a neutral effect of an oral mixed antagonist, bosentan, compared to placebo in the only study of morbidity and mortality. These results have put a brake on the development of this therapeutic class in heart failure.