(Hypertension. 2001;37:170.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Mycophenolate Mofetil Reduces Renal Injury in the Chronic Nitric Oxide Synthase Inhibition Model
From the Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Correspondence to Roberto Zatz, MD, PhD, Laboratório de Fisiopatologia Renal, Av. Dr. Arnaldo, 455, 3-s/3342, 01246–903, São Paulo, SP, Brazil. E-mail rzatz{at}usp.br
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
-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.
Key Words: mycophenolate mofetil • nitric oxide • renal inflammation • renal hemodynamics
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