Endothelin receptors, renal effects and blood pressure

•The endothelin system is a critical renal regulator of salt and water homeostasis.•Renal ETB receptor function is impaired in hypertensive males.•Endothelin increases glomerular permeability to albumin and injures podocytes.•Evidence implicates ETA receptor activation in chronic kidney disease progression.•Clinical use of ETA receptor antagonists still holds promise despite some setbacks.

The endothelin system has emerged as a key player in the renal control of salt and water homeostasis, exerting profound effects on both the renal vasculature and tubular epithelial cells. Recent advances include new actions of endothelins in the glomerulus, an emerging role for the ETA receptor in chronic kidney disease (CKD) progression and in tubular function, and a more detailed understanding of the tubular response to high salt intake. A large body of evidence also implicates dysfunction of the endothelin system in hypertension, particularly salt-sensitive hypertension, although recent data suggests important sex-differences may exist. Finally, clinical trials indicate that antagonists of endothelin receptors hold great promise in treating resistant hypertension and proteinuric renal disease.