Mycophenolate mofetil reduces renal injury in the chronic nitric oxide synthase inhibition model

We and others have recently shown that mycophenolate mofetil (MMF) reduces renal inflammation and glomerular and interstitial injury in the 5/6 renal ablation model. In the present study, we investigated whether MMF limits re nal injury in a model of chronic nitric oxide (NO) inhibition associated wi th a high-salt diet and characterized by progressive systemic hypertension, albuminuria, glomerular sclerosis and ischemia, interstitial expansion, an d progressive macrophage infiltration. Adult male Munich-Wistar rats were d istributed among 3 groups: HS, rats receiving a high-salt diet (3.2% Na); H S+N, HS rats orally treated with the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME), 25 mg . kg(-1) . d(-1); and HS+N+MMF, HS +N rats ora lly treated with MMF, 10 mg . kg(-1) . d(-1). Renal hemodynamics were studi ed after 15 days of treatment; histological and immunohistochemical studies were conducted after 30 days of treatment. MMF treatment did not reverse t he hemodynamic alterations characteristic of this model. Renal injury in th e HS+N group was associated with macrophage and lymphocyte infiltration. Tr eatment with MMF reduced glomerular and interstitial injury and limited mac rophage and lymphocyte infiltration. These results suggest that renal infla mmation is a strong independent factor in the pathogenesis of the nephropat hy associated with the HS+N model.