Mechanisms of ET-1-induced endothelial dysfunction.

There is now increasing evidence that endothelial dysfunction is an early event in the pathophysiology of cardiovascular diseases and can be corrected with certain therapies such as angiotensin converting enzyme inhibitors angiotensin type I receptor antagonists and stains independently of blood pressure lowering effects. Restoring endothelial function appears to be a crucial target since endothelial dysfunction predicts cardiovascular events in various situations such as coronary artery disease peripheral artery disease, or hypertension and in patients undergoing vascular surgery. Preclinical and clinical data strongly support that endothelin receptor antagonists belong to this restricted class of pharmacological agents able to act on the endothelium, and offer a potential therapeutic approach for numerous diseases associated with endothelial dysfunction. The purpose of this review will be therefore, 1) to propose mechanisms by which ET-1 can cause endothelial dysfunction; 2) to provide an overview of pathological situations associated with endothelial dysfunction related to ET-1; and 3) to assemble evidence on efficacy of endothelin receptor antagonists for improvement of endothelial function.