endothelin1mediated

Endothelin-1 mediated refers to the physiological and pathological processes driven by endothelin-1, a potent vasoactive peptide produced mainly by vascular endothelial cells. The EDN1 gene encodes the precursor that is processed to endothelin-1, which circulates in the blood in small amounts and can be stored locally in tissues. Endothelin-1 exerts its effects primarily by binding to two G protein–coupled receptors, endothelin receptor type A (ET_A) and type B (ET_B), which have distinct regional distributions and functional outcomes.

Mechanism and signaling involve synthesis, processing, and receptor engagement. Endothelin-1 is generated from preproendothelin-1 to big endothelin-1 and finally to active endothelin-1 by endothelin-converting enzymes. ET_A receptors are mainly on vascular smooth muscle cells and promote vasoconstriction, cell proliferation, and remodeling through phospholipase C–induced calcium signaling and downstream effectors such as protein kinase C and mitogen-activated protein kinases. ET_B receptors are found on endothelial cells, where their activation can trigger release of nitric oxide and prostacyclin, yielding vasodilation, while ET_B on certain smooth muscle cells can mediate vasoconstriction. The net vascular response depends on receptor distribution, local context, and interacting pathways such as the nitric oxide–prostacyclin system.

Physiologically, endothelin-1 contributes to baseline vascular tone and blood pressure regulation and modulates renal function and tissue perfusion. Pathologically elevated endothelin-1 levels or receptor signaling are implicated in conditions such as pulmonary arterial hypertension, systemic hypertension, and heart failure, where vascular remodeling and inflammation can occur.

Therapeutically, endothelin receptor antagonists, including selective ET_A inhibitors and dual ET_A/ET_B blockers, are used to counteract excessive endothelin-1–mediated vasoconstriction and remodeling in some diseases.