A study in the rat of the renal actions of nitrendipine and diltiazem on the adrenergic regulation of calcium and sodium reabsorption

Abstract

In pentobarbitone-anaesthetized rats, intravenous administration of diltiazem at 5 micrograms kg-1 min-1 did not change blood pressure or renal blood flow but increased glomerular filtration rate by approximately 16%, urine flow by 85%, calcium excretion by 151% and absolute and fractional sodium excretions by 100% and 69%, respectively. A similar pattern of responses was obtained in renally denervated animals, except that calcium excretion did not change statistically. Diltiazem given at 20 micrograms kg-1 min-1 into renally innervated and denervated groups of animals depressed blood pressure between 15-17 mmHg but had no effect on renal haemodynamic or tubular function. Nitrendipine administered at 0.5 microgram kg-1 min-1 to renally innervated and denervated animals significantly depressed blood pressure in intact animals by 6 mmHg and in both groups did not change renal haemodynamics but caused similar increases in urine flow of between 79-98%, calcium excretion of between 87 and 125%, absolute sodium excretion of between 108 and 140% and fractional sodium excretion of between 83 and 170%. Infusion of nitrendipine at 1.0 micrograms kg-1 min-1 into intact or renally denervated animals decreased blood pressure by 18-20 mmHg and increased urine flow by 84-111%, calcium excretion by 85%, absolute sodium excretion by 81-137% and fractional sodium excretion by 52-102%. Stimulation of the renal nerves at low frequencies (0.8 to 1.5 Hz) caused minimal changes in renal haemodynamics but decreased urine flow by 27%, calcium excretion by 35%, absolute and fractional sodium excretions 32% and 36%, respectively. In different groups of animals given either diltiazem at 20 pg kg- I min' or nitrendipine at 0.5 pg kg'- min' or 1.0 fg kg'- min', a similar degree of renal nerve stimulation caused an identical pattern of excretory responses of similar magnitude to those obtained in the absence of drug. 4 The calciuretic, diuretic and natriuretic activities of diltiazem and nitrendipine were not dependent on renal nerves and probably represented a direct action on the tubular reabsorptive processes of these ions. The renal nerve-induced increases in tubular calcium and sodium reabsorption indicate that these alpha-adrenoceptor-mediated responses are not dependent on the inward movement of calcium