Document Detail


Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise.
MedLine Citation:
PMID:  23377961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 VO(2max) 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 Ca(2+) transients) in Ex myocytes to Sed levels. The NOS1 effect on contraction was mediated via greater Ca(2+) 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 (VO(2max), 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.
Authors:
Steve R Roof; Lifei Tang; Joseph E Ostler; Muthu Periasamy; Sandor Györke; George E Billman; Mark T Ziolo
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-04
Journal Detail:
Title:  Basic research in cardiology     Volume:  108     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-07-18     Revised Date:  2014-08-20    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  332     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological*
Animals
Calcium / metabolism
Cardiac Output
Cardiomegaly, Exercise-Induced
Dogs
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Contraction
Myocytes, Cardiac / enzymology*
Nitric Oxide / metabolism
Nitric Oxide Synthase Type I / physiology*
Physical Conditioning, Animal / physiology*
Sedentary Lifestyle
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
K02 HL094692/HL/NHLBI NIH HHS; K02HL094692/HL/NHLBI NIH HHS; R01 HL074045/HL/NHLBI NIH HHS; R01 HL079283/HL/NHLBI NIH HHS; R01HL079283/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
31C4KY9ESH/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nos1 protein, mouse; SY7Q814VUP/Calcium
Comments/Corrections

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