Possible therapeutic role of endothelin antagonists in cardiovascular disease.

Endothelin-1 is an endothelium-derived compound that exerts a variety of hemodynamic and structural alterations in the cardiovascular and pulmonary circuits. The endothelin system is activated in an assortment of disorders and disease states, such as systemic hypertension, pulmonary hypertension, atherosclerosis, acute coronary syndromes, and congestive heart failure. The actions of endothelin are mediated by two types of receptors: ETA and ETB, which are widely distributed in the cardiovascular system. The complexity of biophysical effects mediated by these two types of receptors dictates the therapeutic implications, that is, selective (ETA) versus dual (ETA/ ETB) receptor antagonism. Preliminary experimental and clinical studies reveal a role played by endothelin as a pathogenetic substance and, conversely, a possible role for endothelin antagonism in clinical medicine.