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

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Abstract
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.