The influence of diltiazem and nifedipine on renal function in the rat

1 The effect of intravenous administration of the calcium‐entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone‐anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. 2 Diltiazem was infused at 5, 10 and 20 μg kg −1 min −1 . Blood pressure did not change following 5 μg kg −1 min −1 diltiazem but was significantly reduced, by 12 mmHg, after 10 μg kg −1 min −1 and by 17 mmHg after 20 μg kg −1 min −1 . Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. 3 Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 μg kg −1 min −1 diltiazem, 20% and 24% respectively, by 10 μg kg −1 min −1 diltiazem, but were unchanged by 20 μg kg −1 min −1 . 4 Infusion of nifedipine at 0.5, 1.0 and 2.0 μg kg −1 min −1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 μg kg −1 min −1 only, while g.f.r. did not change at any dose. 5 Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 μg kg −1 min −1 nifedipine, 127%, 197% and 194% respectively, by 1.0 μg kg −1 min −1 , while these variables remained unchanged by a dose of 2.0 μg kg −1 min −1 . 6 These data show that doses on diltiazem and nifedipine, which had little or no effect on blood pressure, had minimal actions on renal haemodynamics. However, at 5 and 10 μg kg −1 min −1 diltiazem and 0.5 and 1.0 μg kg −1 min −1 nifedipine these compounds exhibited direct tubular actions, causing both a diuresis and natriuresis, while at the highest dose of each drug these actions were masked by a concomitant reduction in blood pressure.