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

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. 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