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

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dc.contributor.author Saraiva, Roberto Magalhães [UNIFESP]
dc.contributor.author Minhas, K. M.
dc.contributor.author Raju, SVY
dc.contributor.author Barouch, L. A.
dc.contributor.author Pitz, E.
dc.contributor.author Schuleri, K. H.
dc.contributor.author Vandegaer, K.
dc.contributor.author Li, D. C.
dc.contributor.author Hare, J. M.
dc.date.accessioned 2016-01-24T12:38:10Z
dc.date.available 2016-01-24T12:38:10Z
dc.date.issued 2005-11-29
dc.identifier http://dx.doi.org/10.1161/CIRCULATIONAHA.105.557892
dc.identifier.citation Circulation. Philadelphia: Lippincott Williams & Wilkins, v. 112, n. 22, p. 3415-3422, 2005.
dc.identifier.issn 0009-7322
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/28556
dc.description.abstract 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. en
dc.format.extent 3415-3422
dc.language.iso eng
dc.publisher Lippincott Williams & Wilkins
dc.relation.ispartof Circulation
dc.rights Acesso aberto
dc.subject myocardial infarction en
dc.subject nitric oxide synthase en
dc.subject heart failure en
dc.subject receptors, adrenergic, beta en
dc.title Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction - Role of nitroso-redox equilibrium en
dc.type Artigo
dc.contributor.institution Johns Hopkins Med Inst
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA
dc.description.affiliation Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA
dc.description.affiliation Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil
dc.description.affiliation Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil
dc.identifier.doi 10.1161/CIRCULATIONAHA.105.557892
dc.description.source Web of Science
dc.identifier.wos WOS:000233558300010



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