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Eight healthy volunteers received both oral enalapril (EN; MK-421) 20 mg and placebo (PL) under stable conditions of sodium repletion, 300 mmol sodium/day (HS) and sodium depletion, 10 mmol sodium/day (LS). During PL therapy, fivefold increases in the plasma concentrations of renin and aldosterone were observed when measurements under LS were compared with those under HS conditions. Basal blood pressure (BP) readings were consistently higher and the hypotensive response to EN greater under LS compared with HS conditions. After EN, renal plasma flow increased significantly over the first 4 h, while the glomerular filtration rate, measured both by inulin and creatinine clearances, did not change. A significant natriuretic response was observed within 2 h; further natriuresis between 6 and 12 h after EN was accompanied by increased phosphate excretion.