Endothelin receptor type A (ETA)

Class

Small-molecule selective endothelin A receptor antagonist

Pathway

Endothelin-1/ETA signaling — glomerular injury/proteinuria in CKD, IgA nephropathy, hypertension

Endothelin receptor type A (ETA) is a G protein-coupled receptor found mainly on vascular smooth muscle cells, mesangial cells, and podocytes in the kidney glomerulus. Its natural ligand, endothelin-1, is one of the most potent vasoconstrictor peptides produced by the body, released largely by the endothelium lining blood vessels. Activation of ETA drives smooth muscle contraction, raises blood pressure, and promotes cell proliferation and scar-tissue formation (fibrosis). In the kidney, chronic overactivation of endothelin-1/ETA signaling contributes to elevated pressure within the glomerular filtering units, damage to podocytes, and leakage of protein into urine (proteinuria). This pathway is implicated broadly in chronic kidney disease and specifically in IgA nephropathy, where glomerular injury and scarring drive progressive loss of kidney function, as well as in systemic hypertension. Selective ETA antagonists are designed to block these harmful vasoconstrictive and fibrotic effects while leaving the related ETB receptor, which mediates vasodilation and helps clear endothelin-1 from circulation, largely untouched. This selectivity is intended to preserve beneficial counter-regulatory signaling and limit side effects associated with blocking both receptor subtypes. Modulating ETA is therefore a strategy aimed at reducing proteinuria, slowing glomerular damage, and controlling blood pressure across a range of chronic kidney and cardiovascular conditions.