NIFEDIPINE PREVENTS RENAL INJURY IN RATS WITH CHRONIC NITRIC-OXIDE INHIBITION

Chronic nitric oxide inhibition promotes hypertension, renal dysfuncti on, 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% nifedipi ne 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-omega-nitro-L-arginine methyl ester at 3 mg/kg IV. Renal vasoconstriction and systemic hyper tension induced by the inhibitor were similar in untreated and nifedip ine-treated rats. In a second protocol, eight rats received the nitric oxide inhibitor in their drinking water at 2.6 mmol/L. Eight addition al rats also received nifedipine as above. At day 15, rats given the n itric oxide inhibitor exhibited systemic hypertension and renal vasoco nstriction. Simultaneous nifedipine lowered blood pressure slightly wi thout ameliorating renal hemodynamics. Tail-cuff pressure rose continu ously 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 nifedi pine. At this stage, rats treated with the nitric oxide inhibitor exhi bited 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 su ggest that in the chronic nitric oxide inhibition model, sustained ope ration of voltage-sensitive calcium channels is not essential for rena l vasoconstriction but contributes to systemic hypertension and plays a pivotal role in the development of renal structural injury.