The possible role of endothelin-1 in the pathogenesis of coronary vasospasm.

We investigated the in vivo vasoconstrictor effects of endothelin-1 (ET-1) on canine coronary arteries and the regulation of ET-1 gene expression with special reference to the pathogenesis of coronary vasospasm. ET-1, administered into the coronary arteries of anesthetized dogs, produced a profound and long-lasting reduction in coronary blood flow with myocardial ischemia. Coronary angiography revealed delayed filling of the distal branches and, in some cases, total occlusion in the epicardial portions of coronary arteries. The coronary vasoconstriction induced by ET-1 subsided after intracoronary administration of nitroglycerin. Pretreatment with the Ca2+-channel antagonist, nitrendipine, suppressed ET-1-induced vasoconstriction. In cultured porcine aortic endothelial cells, ET-1 gene expression was induced by agents related to thrombus formation, such as thrombin and transforming growth factor beta (TGF beta). These findings suggest that ET-1, produced by vascular endothelial cells, may contribute to the regulation of coronary circulation and the pathogenesis of coronary vasospasm with respect to intimal injury and subsequent thrombus formation.