CLINICAL-SIGNIFICANCE OF ENDOTHELIN IN CARDIOVASCULAR-DISEASE

Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovascular physiology and pathophysiology. The main endothelin pro duced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular h ypertrophy in salt-dependent models of hypertension (deoxycorticostero ne acetate-salt hypertensive rats, spontaneously hypertensive rats tre ated with deoxycorticosterone acetate and salt, and Dahl salt-sensitiv e rats), and in stroke-prone spontaneously hypertensive rats. In human s, endothelins may play important roles in moderate to severe essentia l hypertension, and in the hypertension of African-Americans. Endothel ins may be involved in cardiac hypertrophy, and there is increasing ev idence of their participation in heart failure, in which acute endothe lin antagonism in humans exerts beneficial effects. Endothelin express ion is enhanced in smooth muscle cells migrating into the intima of ar teries in atherosclerosis, suggesting a role in atherogenesis. Endothe lin may participate as a vasoconstrictor in coronary artery disease, a nd as a contributor to intimal proliferation in restenosis after coron ary angioplasty. in patients with myocardial infarction, cardiac produ ction of endothelin is increased, particularly in those with cardiogen ic shock There is a potential for participation of endothelins in vaso spasm accompanying stroke or subarachnoid hemorrhage; in the latter, e ndothelin antagonism has shown beneficial effects in experimental mode ls. in neonatal and in primary pulmonary hypertension, endothelin expr ession is enhanced, and in experimental models endothelin antagonism r esulted in favorable responses. Systemic sclerosis is another, periphe ral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alter native. The pathophysiologic role of endothelins is becoming increasin gly apparent in cardiovascular disease, generating interesting potenti al therapeutic targets for the use of endothelin antagonists or endoth elin-converting enzyme inhibitors.