endothelint

Endothelin is a potent vasoconstrictor peptide produced by endothelial cells. It plays a significant role in regulating vascular tone and blood pressure. There are three isoforms of endothelin: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). ET-1 is the most widely studied and physiologically important in humans.

The synthesis of endothelin-1 is a multi-step process. It begins with the transcription of the preproendothelin gene, followed by post-translational modifications to produce big endothelin. This precursor peptide is then cleaved by endothelin-converting enzymes (ECEs) to yield the mature and biologically active 21-amino acid peptide.

Endothelin-1 exerts its effects by binding to two distinct G protein-coupled receptors: endothelin receptor type A (ETA) and endothelin receptor type B (ETB). Activation of ETA receptors primarily mediates vasoconstriction and mitogenesis. Activation of ETB receptors has more complex effects, including promoting vasodilation through the release of nitric oxide and prostacyclin, as well as facilitating clearance of endothelin from circulation.

Dysregulation of the endothelin system has been implicated in various cardiovascular diseases, including hypertension, pulmonary arterial hypertension, atherosclerosis, and heart failure. Elevated levels of endothelin-1 are often observed in these conditions, contributing to increased vascular resistance and remodeling. Consequently, endothelin receptor antagonists have been developed and are used clinically for the treatment of certain forms of pulmonary hypertension.