endotelns

Endothelins are a family of potent vasoconstrictor peptides that play a significant role in regulating vascular tone and blood pressure. The endothelin family consists of three distinct isoforms: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). ET-1 is the most abundant and widely studied isoform, primarily produced by endothelial cells lining blood vessels. ET-2 and ET-3 are found in various tissues, including the kidneys, lungs, and gastrointestinal tract.

Endothelins exert their effects by binding to specific receptors on target cells, primarily smooth muscle cells and endothelial cells. There are two main types of endothelin receptors: ETA and ETB. ETA receptors are predominantly found on vascular smooth muscle cells, and their activation leads to vasoconstriction and increased blood pressure. ETB receptors are located on both endothelial and smooth muscle cells. On endothelial cells, ETB receptor activation can stimulate the release of vasodilatory substances like nitric oxide, leading to vasodilation. However, on smooth muscle cells, ETB receptor activation can also contribute to vasoconstriction, depending on the specific physiological context.

Dysregulation of the endothelin system has been implicated in the pathogenesis of several cardiovascular diseases, including hypertension, pulmonary hypertension, atherosclerosis, and heart failure. Elevated levels of endothelin-1 are often observed in these conditions, contributing to excessive vasoconstriction, vascular remodeling, and inflammation. Consequently, endothelin receptor antagonists (ERAs) have been developed as therapeutic agents for conditions such as pulmonary arterial hypertension, where they block the vasoconstrictive effects of endothelins.