Endothelin-1 and atherosclerosis: potential complications associated with endothelin-receptor blockade

Atherosclerotic vascular disease retrains the single most prevalent cause of death and morbidity in the western world. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that also possesses mitogenic activity on many cell types. including vascular smooth muscle cells. Raised plasma and tissue levels of ET-1 have been described in atherosclerosis in animal models and in man, suggesting that this peptide plays a pathopliysiological role in this condition. Two main ET-1 receptors hate been cloned (ETA and ETB). Mixed ETA B and receptor subtype selective antagonists Lire now available. Since ET-1 is generally believed to be a `pathophysiological peptide', we discuss the therapeutic potential of ET-1 antagonists in atherosclerosis and consider whether, at certain sites in this process. ET-1 may play a beneficial role. In such situations ET antagonism tray be undesirable. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.