Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction - Role of nitroso-redox equilibrium

Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction - Role of nitroso-redox equilibrium

Autor Saraiva, Roberto Magalhães Autor UNIFESP Google Scholar
Minhas, K. M. Google Scholar
Raju, SVY Google Scholar
Barouch, L. A. Google Scholar
Pitz, E. Google Scholar
Schuleri, K. H. Google Scholar
Vandegaer, K. Google Scholar
Li, D. C. Google Scholar
Hare, J. M. Google Scholar
Instituição Johns Hopkins Med Inst
Universidade Federal de São Paulo (UNIFESP)
Resumo Background - Neuronal nitric oxide synthase ( NOS1) plays key cardiac physiological roles, regulating excitation-contraction coupling and exerting an antioxidant effect that maintains tissue NO- redox equilibrium. After myocardial infarction ( MI), NOS1 translocates from the sarcoplasmic reticulum to the cell membrane, where it inhibits beta- adrenergic contractility, an effect previously predicted to have adverse consequences. Counter to this idea, we tested the hypothesis that NOS1 has a protective effect after MI.Methods and Results - We studied mortality, cardiac remodeling, and upregulation of oxidative stress pathways after MI in NOS1- deficient ( NOS1 -/ -) and wild- type C57BL6 ( WT) mice. Compared with WT, NOS1 -/ - mice had greater mortality ( hazard ratio, 2.06; P = 0.036), worse left ventricular ( LV) fractional shortening ( 19.7 +/- 1.5% versus 27.2 +/- 1.5%, P < 0.05), higher LV diastolic diameter ( 5.5 +/- 0.2 versus 4.9 +/- 0.1 mm, P < 0.05), greater residual cellular width ( 14.9 +/- 0.5 versus 12.8 +/- 0.5 mu m, P < 0.01), and equivalent beta- adrenergic hyporesponsiveness despite similar MI size. Superoxide production increased after MI in both NOS1 -/ - and WT animals, although NO increased only in WT. NADPH oxidase ( P < 0.05) activity increased transiently in both groups after MI, but NOS1 -/ - mice had persistent basal and post- MI elevations in xanthine oxidoreductase activity.Conclusions - Together these findings support a protective role for intact NOS1 activity in the heart after MI, despite a potential contribution to LV dysfunction through beta- adrenergic hyporesponsiveness. NOS1 deficiency contributes to an imbalance between oxidative stress and tissue NO signaling, providing a plausible mechanism for adverse consequences of NOS1 deficiency in states of myocardial injury.
Palavra-chave myocardial infarction
nitric oxide synthase
heart failure
receptors, adrenergic, beta
Idioma Inglês
Data de publicação 2005-11-29
Publicado em Circulation. Philadelphia: Lippincott Williams & Wilkins, v. 112, n. 22, p. 3415-3422, 2005.
ISSN 0009-7322 (Sherpa/Romeo, fator de impacto)
Publicador Lippincott Williams & Wilkins
Extensão 3415-3422
Fonte http://dx.doi.org/10.1161/CIRCULATIONAHA.105.557892
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000233558300010
Endereço permanente http://repositorio.unifesp.br/handle/11600/28556

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