Effect of nifedipine on urinary concentrating ability: a placebo controlled study.

A placebo-controlled, randomized, crossover study was conducted to assess a possible effect of a dihydropyridine Ca-entry blocker, nifedipine, on urinary concentration ability in nine healthy men under a water-deprivated condition. Placebo and nifedipine (20 mg) were orally administered on two separate occasions, at least one week apart, after the urinary osmolarity was stabilized. Urinary osmolarity, osmolar clearance, negative free water clearance, urine volume, urinary solutes (Na, K and urea), creatinine clearance and plasma vasopressin (AVP) were measured during the postdose 3-hour period and compared with those during the respective predose (baseline) period. Urinary osmolarity decreased by nifedipine from 1047.2 ± 34.4 to 873.0 ± 38.3 mOsm/kg (mean ± SEM) at 2 hours postdose (P < 0.05). Mean % decrease in urinary osmolarity at 1 to 3 hours after nifedipine was significantly (P < 0.01) greater than after placebo. Urine volume significantly (P < 0.01) increased from the baseline of 0.49 ± 0.06 to 1.1 ± 0.15 ml/min at 2 hours after nifedipine. Relationship between osmolar clearance and negative free water clearance relative to glomerular filtration rate observed during the postnifedipine phase was significantly (P < 0.01) shifted downward compared with that derived from the pooled data unrelated to nifedipine dosing. No significant drug effect was detected on plasma AVP. Both placebo and nifedipine dosed during the continued water deprivation and stabilized urinary osmolarity condition caused an increase in the urinary excretions of solutes. The results indicate that nifedipine inhibits urinary concentration. This does not appear to be due to the inhibition of AVP secretion from the hypophysis. However, the possibility that nifedipine might inhibit the action of AVP at renal collecting tubules cannot be negated. In addition, whether the observed natri- and kaliuresis would be due to placebo or water deprivation (or both) requires further studies.