ROLE OF INTRARENAL ENDOTHELIN IN THE GENERATION AND MAINTENANCE OF HYPERTENSION

Alterations in the renal metabolism and/or actions of endothelin-1 (ET -1) may be involved in the pathogenesis and maintenance of essential a nd renal parenchymal hypertension. ET-1 has the potential to modify a broad range of renal functions involved in controlling systemic blood pressure. First, the kidney clears a large percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute to hypertension occurring in the setting of chronic renal failure. Second, ET-1 potent ly constricts the renal vasculature resulting in increased fluid reten tion and possibly contributing to glomerular sclerosis; enhanced renal vascular and glomerular ET-1 production and target cell actions may p lay a role in essential hypertension or hypertension accompanying chro nic renal failure, cyclosporine administration, or erythropoietin ther apy. Lastly, ET-1 is also an autocrine inhibitor of collecting duct so dium and water reabsorption; reduced nephron ET-1 production may resul t in fluid retention in essential hypertension. Determination of the t rue role that ET-1 plays in the pathogenesis of the varied forms of hy pertension awaits the development of safe, potent, and specific endoth elin antagonists.