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Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise

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Abstract

Exercise results in beneficial adaptations of the heart that can be directly observed at the ventricular myocyte level. However, the molecular mechanism(s) responsible for these adaptations are not well understood. Interestingly, signaling via neuronal nitric oxide synthase (NOS1) within myocytes results in similar effects as exercise. Thus, the objective was to define the role NOS1 plays in the exercise-induced beneficial contractile effects in myocytes. After an 8-week aerobic interval training program, exercise-trained (Ex) mice had higher VO2max and cardiac hypertrophy compared to sedentary (Sed) mice. Ventricular myocytes from Ex mice had increased NOS1 expression and nitric oxide production compared to myocytes from Sed mice. Remarkably, acute NOS1 inhibition normalized the enhanced contraction (shortening and Ca2+ transients) in Ex myocytes to Sed levels. The NOS1 effect on contraction was mediated via greater Ca2+ cycling that resulted from increased phospholamban phosphorylation. Intriguingly, a similar aerobic interval training program on NOS1 knockout mice failed to produce any beneficial cardiac adaptations (VO2max, hypertrophy, and contraction). These data demonstrate that the beneficial cardiac adaptations observed after exercise training were mediated via enhanced NOS1 signaling. Therefore, it is likely that beneficial effects of exercise may be mimicked by the interventions that increase NOS1 signaling. This pathway may provide a potential novel therapeutic target in cardiac patients who are unable or unwilling to exercise.

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Acknowledgments

This work was supported by the National Institutes of Health (K02HL094692, R01HL079283, M. T. Ziolo).

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  1. Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210, USA

    Steve R. Roof, Lifei Tang, Joseph E. Ostler, Muthu Periasamy, Sandor Györke, George E. Billman & Mark T. Ziolo

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Roof, S.R., Tang, L., Ostler, J.E. et al. Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise. Basic Res Cardiol 108, 332 (2013). https://doi.org/10.1007/s00395-013-0332-6

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