Endothelin A receptor

Class

Selective endothelin A receptor antagonist

The endothelin A receptor (ETA) is a G-protein-coupled receptor found mainly on vascular smooth muscle cells. It is activated by endothelin-1, a peptide hormone produced by the vascular endothelium that is among the most potent vasoconstrictors identified. Binding of endothelin-1 to ETA triggers smooth muscle contraction, raising blood pressure locally and systemically, and over time promotes cell proliferation and fibrous tissue deposition. Selective ETA antagonists block this action while sparing the related endothelin B receptor (ETB), which sits largely on endothelial cells and mediates vasodilation and clearance of circulating endothelin-1. This selectivity is deliberate: blocking ETA lowers vascular resistance and limits proliferative and fibrotic signaling, while leaving ETB-mediated vasodilation and endothelin clearance intact, which is thought to reduce fluid retention compared with agents that block both receptor subtypes. This mechanism is relevant across several disease areas where excess endothelin signaling contributes to pathology: pulmonary arterial hypertension, chronic kidney disease with proteinuria (including diabetic kidney disease), and certain fibrotic and oncologic conditions where endothelin drives tissue remodeling or supports tumor vasculature.