Endothelins in chronic cardiac failure.

The endothelins are a family of three structurally related peptides. Endoth elin-l (ET-1) is formed from the big endothelin by the action of the endoth elin 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 : pos itive inotropism and stimulation of cell growth, for example. Endothelin is found in the general circulation but its role is mainly local in maintaini ng vascular tone. The endothelin system is activated in cardiac failure and increased concent rations of plasma endothelin increased, ET-1 converting enzyme and increase d density of endothelin receptors are observed. The action of the endotheli n 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 prop erties of endothelin, inhibition of its action might be particularly useful in patients with cardiac failure. Its action can be blocked either by prev enting its synthesis by inhibiting the endothelin converting enzyme or by b locking 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 c linical trials.