Effects of enalapril on renal sodium handling in healthy subjects on low, intermediate, and high sodium intake

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have a modest natriuretic effect, but the responsible changes in tubular sodium (Na) handling are not fully known. We therefore studied the effect of a single dose of 20 mg enalapril on Na excretion in 8 healthy subjects, using lithium clearance and maximal water diuresis to analyze tubular Na handling. Because the natriuretic effect may depend on the volume state, the same subjects were studied during low (20 mmol Na/day), medium (200 mmol Na/day), and high (400 mmol Na/day) salt intake. Enalapril caused natriuresis during the 20-mmol Na diet (from 51 +/- 9 to 81 +/- 14 mumol/min, p < 0.05) and the 200-mmol Na diet (from 190 +/- 24 to 230 +/- 31 mumol/min, p < 0.05), but not during the 400-mmol Na diet. The increase in Na excretion was not accompanied by consistent changes in glomerular filtration rate (GFR), free water clearance data, maximal urine flow, uric acid clearance, or lithium clearance. Instead, the increase in Na excretion was positively related to the increase in Na concentration in the maximally diluted urine (r = 0.75, p < 0.01). Regardless of diet, enalapril reduced the filtration fraction, but a significant increase in effective renal plasma flow was noted only during the 20-mmol Na diet. The data suggest that a decrease in Na reabsorption in the diluting segment, perhaps related to renal vasodilatation, participates in the natriuretic effect of ACE inhibition in humans.