endotheline

Endotheline is not a widely used term in modern pharmacology; it is likely a misspelling of endothelin, a family of potent vasoactive peptides produced by endothelial cells. Endothelins regulate vascular tone and play roles in cardiovascular and renal physiology. The best studied member is endothelin-1 (ET-1), a 21-amino-acid peptide generated from its precursor preproendothelin-1. The EDN1 gene encodes ET-1; the active peptide is produced after processing of Big ET-1 by endothelin-converting enzyme (ECE).

Endothelins exert their effects via G protein–coupled endothelin receptors, primarily ETA (ET_A) and ETB (ET_B). ETA receptors on vascular smooth muscle mediate potent vasoconstriction and cell proliferation. ETB receptors are found on both endothelial and smooth muscle cells; endothelial ETB activation promotes the release of nitric oxide and prostacyclin (vasodilation) and contributes to clearance of ET-1, while smooth muscle ETB can contribute to vasoconstriction in some vascular beds.

Physiologically, endothelins help regulate vascular tone, blood pressure, and regional blood flow, and they influence renal sodium handling and cardiac development. Pathologically elevated endothelin activity has been linked to hypertension, heart failure, and pulmonary arterial hypertension.

Therapeutically, endothelin receptors antagonists such as bosentan, ambrisentan, and macitentan are used to treat PAH and certain other conditions. These agents differ in receptor selectivity and safety profiles, including concerns about liver toxicity and, for some drugs, pregnancy risk.