Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/74248
Type: Artigo de periódico
Title: Simvastatin prevents load-induced protein tyrosine nitration in overloaded hearts
Author: Nadruz, W
Lagosta, VJ
Moreno, H
Coelho, OR
Franchini, KG
Abstract: Hydroxymethylglutaryl-coenzyme A reductase inhibitors prevent load-induced left ventricular hypertrophy (LVH). Whether this effect is related to antioxidant properties of this class of drugs is poorly understood. The aim of the present report was to evaluate the regulation of nitrotyrosine production during the development of load-induced LVH and the effect of simvastatin treatment in this process. Rats were subjected to aortic constriction up to 15 days. LVH was evaluated by left/right ventricle mass ratio. Myocardial content of nitrotyrosine, nitric oxide synthase ( NOS) isoforms, and phagocyte-type NAD(P)H-oxidase subunits (p67-phox and p22-phox) were analyzed by immunoblotting and immunohistochemistry assays. Another group of rats received treatment with either simvastatin or placebo for 15 days after the onset of pressure overload, and their hearts were also studied. Myocardial nitrotyrosine content was increased from 3 to 15 days of pressure overload in regions of cardiac myocytes in close apposition to myocardial stroma during LVH. Neuronal NOS ( nNOS), inducible NOS ( iNOS), and endothelial NOS ( eNOS) isoforms had their expression increased in coronary vessels ( nNOS and iNOS) and in myocardial stroma ( eNOS) from day 3 to day 7 of aortic constriction. However, p67-phox and p22-phox expression was increased in cells of myocardial stroma in parallel to augmented myocardial nitrotyrosine content. Simvastatin treatment inhibited the increases in myocardial nitrotyrosine content and in p67-phox and p22-phox expression, and significantly reduced LVH. In conclusion, antioxidant properties of simvastatin might play a role in myocardial remodeling induced by pressure overload.
Subject: hypertrophy
cardiac function
heart
oxidative stress
statins
Country: EUA
Editor: Lippincott Williams & Wilkins
Rights: fechado
Identifier DOI: 10.1161/01.HYP.0000124252.43470.2c
Date Issue: 2004
Appears in Collections:Unicamp - Artigos e Outros Documentos

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