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Endothelins and anti-endothelins.

Endothelins, endothelin-1 (ET1), endothelin-2 (ET2) and endothelin-3 (ET3), are the most potent vasoconstrictor peptides released by endothelial cells. ET production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products and cytokines, whereas nitric oxide and prostacyclin reduce ET production. ET bind to ETA and ETB receptors and produce marked and sustained rise in blood pressure, intense vasoconstriction of coronary arteries and have positive inotropic and chronotropic effects on myocardium. Besides, they influence neuroendocrine, renal and smooth muscle functions. ET appears to function mostly as a paracrine or an autocrine hormone. ET may have a role in hypertension, atherosclerosis, heart failure, coronary artery disease, renal insufficiency, vascular hypertrophy, respiratory and cerebrovascular conditions. Several antagonists of ET acting at receptor level or influencing endothelin converting enzyme (ECE) are under investigation and have great potential as agents for use in the treatment of wide spectrum of disease entities and as biologic probes for understanding the actions of ET in human beings.