[Endothelins in chronic cardiac insufficiency].

The endothelins are a family of three structurally related peptides. Endothelin-1 (ET-1) is formed from the big endothelin by the action of the endothelin converting enzyme. It acts on two types of receptor, ETA and ETB. ET-1 is a powerful vasoconstrictor but also has a number of other effects: positive inotropism and stimulation of cell growth, for example. Endothelin is found in the general circulation but its role is mainly local in maintaining vascular tone. The endothelin system is activated in cardiac failure and increased concentrations of plasma endothelin increased, ET-1 converting enzyme and increased density of endothelin receptors are observed. The action of the endothelin system and its relationships with other neuro-hormonal systems activated in cardiac failure are not fully understood but research is under way which should clarify these mechanisms in the next few years. In view of the properties of endothelin, inhibition of its action might be particularly useful in patients with cardiac failure. Its action can be blocked either by preventing its synthesis by inhibiting the endothelin converting enzyme or by blocking the endothelin receptor. Endothelin receptor blockade is associated with beneficial haemodynamic changes, an action on ventricular remodelling and possibly an improved prognosis. Many substances, either selective for ETA receptors or mixed ETA and ETB receptor blockers, are under development. The benefits of these products will require confirmation by large scale clinical trials.