Diuretic and natriuretic effects of nifedipine on isolated perfused rat kidneys

M Marre, J Misumi, KD Raemsch, P Corvol and J Menard

The effects of nifedipine, a vasodilating drug which acts through calcium antagonism, were studied in vitro using isolated perfused rat kidneys. Most of the nifedipine was neither metabolized nor excreted by this preparation. Four doses were tested: 50, 250, 500 and 750 nM. The two higher concentrations enhanced urine flow and sodium (UNaV) and potassium excretion. Tubular reabsorption of sodium was reduced compared to untreated control kidneys. The glomerular filtration rate was not modified but the filtration fraction decreased. The magnitude of urine volume, UNaV, urinary potassium excretion and filtration fraction changes were related to the dose of nifedipine. The decrement of total renal resistance and the increment of UNaV were correlated for 500 and 750 nM nifedipine (n = 13; r = -0.77; P less than .001), suggesting that it acted by dilating the renal vascular bed. Nifedipine at 250, 500 and 750 nM significantly increased the renin secretion rate compared to that of untreated control kidneys. When renin secretion was enhanced by 50 nM isoproterenol, this stimulatory effect was enhanced in kidneys concomitantly treated with 500 and 750 nM nifedipine. Dihydralazine, another vasodilating drug, was tested at a comparable molar dose (500 nM) and induced similar changes in urine volume, UNaV, urinary potassium excretion and Na reabsorption. The variations in total renal resistance and UNaV were also inversely correlated (n = 8; r = -0.68; P less than .05). Dihydralazine did not modify renin secretion rate significantly. These results suggest that: 1) both nifedipine and dihydralazine increase diuresis, natriuresis and kaliuresis in the isolated perfused rat kidney and 2) nifedipine enhances basal renin release from the juxta-glomerular cells and potentiates renin release caused by beta receptor stimulation.

Volume 223, Issue 1, pp. 263-270, 10/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics

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