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Endothelin-1 (ET-1) is a vasoconstrictor peptide of endothelial origin belonging to a family of four isopeptides consisting of ET-1, ET-2, ET-3, and vasoactive intestinal constrictor also called ET-4. These peptides show considerable homology with the sarafotoxins which are cardiotoxic molecules present in the venom of the snake Israeli burrowing asp. ET-1 is the most potent vasoconstrictor known, ten times more potent than angiotensin II. It is synthesized in response to stress, hypoxia, and other vasoactive substances. The physiological role of the endothelins and site of synthesis for ET-2 and ET-3 are still unknown. Two endothelin receptors have been cloned. Elevated plasma levels of ET-1 have been measured in patients suffering from various diseases such as myocardial infarction, cardiogenic shock, septic shock, renal failure, subarachnoid haemorrhage and pre-eclampsia. ET-receptor antagonists and ET-1 synthesis inhibitors are now available. It has been shown that these inhibitors, and also ET-1 antibodies, ameliorate the consequences of severely impaired blood flow in the kidney and in the brain. In animals, infusion of endothelin antibody has been shown to limit the size of myocardial infarction. ET-1 inhibitors can be expected to play a therapeutic role in the future.

Endothelin is a newly discovered potent vasoconstrictive polypeptide released by endothelial cells in response to various stimuli, including vasoactive peptides such as angiotensin II, adrenaline and vasopressin, and thrombocyte products like transforming beta growth factor and thrombin. Endothelin is believed to exert its main effects locally, in a paracrine or autocrine way. In vascular tissue, endothelin induces longlasting contraction of smooth muscle cells, leading to decreased blood flow, especially in the coronary and renal circulation, together with an increase in systemic blood pressure. It acts also mitogenically in vascular smooth muscle cells. Endothelin stimulates release of aldosterone and catecholamines in non-vascular tissue, and inhibits release of renin. A physiological function of endothelin may be to modulate vascular tone, and increased levels of circulating endothelin are seen after the "cold pressor test". Moreover, plasma endothelin concentration is elevated during acute myocardial infarction, in acute renal failure, in patients with hypertension, and during cardiogenic chock. What role endothelin plays in the development of these conditions, and in other disorders such as vascular spasm and atherosclerosis is uncertain.