title: Mycophenolate Mofetil Reduces Renal Injury in the Chronic Nitric Oxide Synthase Inhibition Model.
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(omega)-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.
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.forename: Denise Maria
authors.initials: DM
authors.lastname: Avancini Costa Malheiros
authors.forename: Irene
authors.lastname: de Lourdes Noronha
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz