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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2001, Vol.37 (1), p.170-175
• Main Authors: FUJIHARA, Clarice Kazue, AVANCINI COSTA MALHEIROS, Denise Maria, NORONHA, Irene De, DE NUCCI, Gilberto, ZATZ, Roberto
• Format: Article
• Language: English
• Subjects: Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.37.1.170

-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.