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

Roberto M. Saraiva, Khalid M. Minhas, Shubha V Y Raju, Lili Barouch, Eleanor Pitz, Karl H. Schuleri, Koenraad Vandegaer, Dechun Li, Joshua M. Hare

Research output: Contribution to journalArticle


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 β-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-/- and WT animals, although NO increased only in WT. NADPH oxidase (P-/- 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 β-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.

Original languageEnglish (US)
Pages (from-to)3415-3422
Number of pages8
Issue number22
Publication statusPublished - Nov 2005



  • Heart failure
  • Myocardial infarction
  • Nitric oxide synthase
  • Receptors, adrenergic, beta

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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