Mycophenolate Mofetil Reduces Renal Injury in the Chronic Nitric Oxide Synthase Inhibition Model

Abstract

Abstract —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 renal injury in a model of chronic nitric oxide (NO) inhibition associated with a high-salt diet and characterized by progressive systemic hypertension, albuminuria, glomerular sclerosis and ischemia, interstitial expansion, and progressive macrophage infiltration. Adult male Münich-Wistar rats were distributed among 3 groups: HS, rats receiving a high-salt diet (3.2% Na); HS+N, HS rats orally treated with the NO inhibitor N ^ω -nitro- l -arginine methyl ester (L-NAME), 25 mg · kg ⁻¹ · d ⁻¹ ; and HS+N+MMF, HS+N rats orally treated with MMF, 10 mg · kg ⁻¹ · d ⁻¹ . Renal hemodynamics were studied after 15 days of treatment; histological and immunohistochemical studies were conducted after 30 days of treatment. MMF treatment did not reverse the hemodynamic alterations characteristic of this model. Renal injury in the HS+N group was associated with macrophage and lymphocyte infiltration. Treatment with MMF reduced glomerular and interstitial injury and limited macrophage and lymphocyte infiltration. These results suggest that renal inflammation is a strong independent factor in the pathogenesis of the nephropathy associated with the HS+N model.