Nitrendipine and Renal Tubular Function in Human Volunteers

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Abstract
Nine normotensive, water‐loaded subjects received 10 mg oral nitrendipine, and eight subjects received placebo in a double‐blind randomized manner. Urine and plasma were collected at fixed time points for 1 hour before and for 4 hours after drug administration for biochemical measurements. Glomerular filtration rate was measured by inulin clearance and effective renal blood flow was measured by para‐amino hippurate clearance. Absolute sodium excretion increased by 25.9% from 0.27 ± 0.03 mmol/min to 0.34 ± 0.02 mmol/min (P = .02), and fractional sodium excretion increased by 32.3% from 18.9 ± 3.0% to 25.0 ± 1.9% (P = .03) after nitrendipine, but both were unchanged after placebo. There was no change in inulin clearance, para‐amino hippurate clearance, urine volume, or fractional excretion of uric acid, which made an effect on glomerular filtration, renal blood flow, or proximal tubular junction an unlikely explanation of the natriuresis. Fractional excretion of magnesium increased after both placebo and nitrendipine administration, from 5.0 ± 0.6% to 6.8 ± 0.7% (P = .027) and 5.7 ± 0.8% to 8.8 ± 1.0% (P = .006), respectively. Fractional excretion of phosphate also increased after both placebo and nitrendipine, from 9.5 ± 2.3% to 12.9 ± 3.9% (P =.05) and 9.7 ± 1.7% to 14.2 ± 1.9% (P = .002), respectively. These changes are likely to be due to the effects of the water load rather than due to a drug effect. There was no change in clearance of solute free water, which made a direct effect on the loop of Henle or cortical diluting segment unlikely. Fractional excretion of potassium (FEK%) appeared to be inhibited by the water load in both groups. FEK% decreased by 24.2% from 5.8 ± 0.3% to 4.4 ± 0.3% (P = .009) after nitrendipine administration and by 34.8% from 6.9 ± 0.8% to 4.5 ± 0.3% (P = .04) after placebo administration. The continuing natriuresis in the face of potassium retention may indicate a distal tubular action of nitrendipine.