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(Hypertension. 1995;26:150-155.)
© 1995 American Heart Association, Inc.

Articles

Nifedipine Prevents Renal Injury in Rats With Chronic Nitric Oxide Inhibition

Presented in part at the 26th Congress of the American Society of Nephrology, Boston, Mass, November 14-17, 1993, and published in abstract form (J Am Soc Nephrol. 1993;4:520).

Miriam Oliveira Ribeiro; Edson Antunes; Marcelo Nicolas Muscará; Gilberto De Nucci; Roberto Zatz

From the Renal Division, Department of Clinical Medicine, University of São Paulo (Brazil) School of Medicine, and Department of Pharmacology, State University of Campinas (Brazil) School of Medicine.

Correspondence to Roberto Zatz, MD, PhD, Laboratório de Fisiopatologia Renal, Av. Dr. Arnaldo, 455, 3-s/67, 01246-903 São Paulo SP, Brazil.

Abstract Chronic nitric oxide inhibition promotes hypertension, renal dysfunction, and renal injury by unclear mechanisms. We examined the effects in this model of concomitant treatment with the calcium channel blocker nifedipine. Six adult male Munich-Wistar rats received 0.025% nifedipine in chow. Six untreated rats served as controls. Fifteen days later, renal function was evaluated in anesthetized rats before and after a bolus injection of the nitric oxide inhibitor N-nitro-L-arginine methyl ester at 3 mg/kg IV. Renal vasoconstriction and systemic hypertension induced by the inhibitor were similar in untreated and nifedipine-treated rats. In a second protocol, eight rats received the nitric oxide inhibitor in their drinking water at 2.6 mmol/L. Eight additional rats also received nifedipine as above. At day 15, rats given the nitric oxide inhibitor exhibited systemic hypertension and renal vasoconstriction. Simultaneous nifedipine lowered blood pressure slightly without ameliorating renal hemodynamics. Tail-cuff pressure rose continuously in rats receiving the nitric oxide blocker, reaching 171±7 mm Hg at 30 days, but remained at 143±3 mm Hg in rats also given nifedipine. At this stage, rats treated with the nitric oxide inhibitor exhibited extremely variable plasma renin activity, tuft collapse in 10.1±2.2% of the glomeruli, and renal interstitial fibrosis. Simultaneous nifedipine treatment normalized the dispersion of plasma renin levels, while preventing renal morphological abnormalities. These results suggest that in the chronic nitric oxide inhibition model, sustained operation of voltage-sensitive calcium channels is not essential for renal vasoconstriction but contributes to systemic hypertension and plays a pivotal role in the development of renal structural injury.

Key Words: nitric oxide • channel blockers, calcium • kidney • blood pressure • nephritis, interstitial • kidney glomerulus

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