A nitric oxide-generating beta-blocking agent prevents renal injury in the rat remnant kidney model. Comparative study of two beta-blocking drugs, nipradilol and propranolol.

Background: The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether (3-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. Methods: Nipradilol, a (3-blocker with an ONO 2 group (5, 10 or 15 mg/kg/ day) and propranolol, a (3-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U NOx ) and cyclic GMP (U cGMP ). Results: Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U NOx in comparison with the sham-operated rats. Nipradilol increased U NOx and U cGMP significantly and in a dose-dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U NOx . The addition of nipradilol increased U NOx and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. Conclusion: These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The β-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.