title: Obligatory role of neuronal nitric oxide synthase in the heart's antioxidant adaptation with exercise.
abstract: Excessive oxidative stress in the heart results in contractile dysfunction. While antioxidant therapies have been a disappointment clinically, exercise has shown beneficial results, in part by reducing oxidative stress. We have previously shown that neuronal nitric oxide synthase (nNOS) is essential for cardioprotective adaptations caused by exercise. We hypothesize that part of the cardioprotective role of nNOS is via the augmentation of the antioxidant defense with exercise by positively shifting the nitroso-redox balance. Our results show that nNOS is indispensable for the augmented anti-oxidant defense with exercise. Furthermore, exercise training of nNOS knockout mice resulted in a negative shift in the nitroso-redox balance resulting in contractile dysfunction. Remarkably, overexpressing nNOS (conditional cardiac-specific nNOS overexpression) was able to mimic exercise by increasing VO2max. This study demonstrates that exercise results in a positive shift in the nitroso-redox balance that is nNOS-dependent. Thus, targeting nNOS signaling may mimic the beneficial effects of exercise by combating oxidative stress and may be a viable treatment strategy for heart disease.
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roof
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Hsiang-Ting
authors.initials: HT
authors.lastname: Ho
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Little
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Ostler
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Brundage
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Villamena
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Sandor
authors.initials: S
authors.lastname: Györke
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Biesiadecki
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.affiliation: Department of Physiology, Cardiovascular Research Center, Temple University, Philadelphia, PA, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA. Electronic address: ziolo.1@osu.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D061251:Primary Cell Culture; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000099211:Phospholamban; C496321:Nos1 protein, mouse
keywords: Exercise; Nitroso–redox balance; Phosphatase; Phospholamban; ROS