Endothelins in hypertension and kidney diseases

Endothelin-1 (ET-1) is the most potent vasoconstrictor known. Disturbances in the renal release and/or actions of ET-1 are involved in the pathogenesis and maintenance of essential and renal parenchymal hypertension. In animal models of disease evidence is presented for ET playing a role in the pathogenesis of some renal diseases: acute renal failure, ciclosporine nephrotoxicity, radiocontrast nephrotoxicity, glomerulonephritis, diabetic nephropathy and renal glomerulosclerosis. The studies in humans have been restricted to measurements of ET levels in blood and urine, and therefore determination of its true role in the pathogenesis of arterial hypertension and kidney diseases must await the development of safe, potent and highly selective ETA and ETB receptor antagonists as well as selective ETB receptor agonists. These compounds could become therapeutic agents in the future. The use of ET converting enzyme inhibitors may also become an important modality for treatment of diseases linked with increased ET production.