What is endothelin?
Endothelin is a peptide produced in the vascular endothelium, and is centrally involved in blood pressure regulation. Smooth muscle cells in the blood vessel are directly responsible for mediating vessel diameter. The regulation of blood flow depends on a delicate balance between physical and chemical stimuli that cause smooth muscle cells to dilate or constrict. Chronic periods of excessive vasoconstriction in the peripheral circulation can lead to disturbances in blood pressure (hypertension) or heart function (congestive heart failure), whereas acute episodes of intense vasoconstriction (vasospasm) can restrict blood flow, leading to severe tissue damage and organ failure (myocardial infarction or kidney failure). Endothelin antagonists have demonstrated additional benefits in preclinical tests when used with existing therapies.

Endothelin exerts its influence by binding to specific receptors, of which there are two primary types, ETAand ETB. When endothelin binds to the ETA receptors in a blood vessel, it induces powerful vasoconstriction; when it binds to the ETB receptors, it mediates vasodilation. Thus an ETA antagonist could inhibit the excessive vasoconstrictive effect of endothelin, while preserving the vasodilative effect of endothelin at the ETB receptors.