Endothelin ET A Receptor Blockade With Darusentan Increases Sodium and Potassium Excretion in Aging Rats

This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na + , K + -ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P