The rise and fall of endothelin receptor antagonists in congestive heart failure.

S ince its discovery in 1988 [1], the role of endothelin in cardiovascular disease has been intensively studied. Activation of the endothelin system is considered part of the neurohormonal response in congestive heart failure. Endothelin is produced by vascular endothelial cells and has potent vasoconstrictor effects [2]. Elevated endothelin levels induce adverse cardiac remodelling and cause progressive aggravation of congestive heart failure by influencing loading conditions of the heart and by reducing coronary flow; endothelin also has direct (toxic) myocardial effects [2]. Several clinical studies have demonstrated that higher plasma levels of endothelin-1 correlates with the degree of haemodynamic and functional impairment, and worse prognosis in heart failure [3–6].