title: Nitric oxide synthase inhibition abolishes exercise-mediated protection against isoproterenol-induced cardiac hypertrophy in female mice.
abstract: OBJECTIVE
  Exercise training (ET) provides a cardioprotective effect against pathological cardiac hypertrophy. Nitric oxide (NO) plays an important role in modulating cardiac hypertrophy. However, few studies explore the relationship between NO signaling and the inhibitory effect of ET on pathological cardiac remodeling.
  
  
  METHODS
  In this study, we evaluated ET effects on isoproterenol (ISO)-induced cardiac hypertrophy in female mice. Moreover, L-NAME (Nω-nitro-L-arginine methyl ester), a nonselective NO synthase (NOS) inhibitor, was used to assess the involvement of NO signaling in cardiac hypertrophy. Morphological and echocardiographic variables were assessed. Cardiac hypertrophy-related gene expression was detected by real-time PCR and the protein levels of NOS signaling molecules were determined by Western blot.
  
  
  RESULTS
  L-NAME treatment prevented the beneficial effects of ET against the increase in heart weight (HW)/body weight (BW), HW/tibia length and lung weight/BW and echocardiographic variables following ISO injection. Also, L-NAME co-administration reversed ET-induced inhibition of myocardial fibrosis and fetal gene reactivation in ISO-treated mice. Furthermore, L-NAME treatment prevented ET-mediated up-regulation of phosphorylated endothelial NOS and plasma NO in ISO-treated mice.
  
  
  CONCLUSIONS
  Our findings demonstrate that L-NAME treatment could abolish ET-induced cardioprotection against pathological cardiac hypertrophy and that NOS modulation may be involved in the antihypertrophic effects induced by ET.
authors.forename: Jiling
authors.initials: J
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Wencong
authors.initials: W
authors.lastname: Tian
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D007545:Isoproterenol / Q000009:adverse effects; D051379:Mice; D009206:Myocardium / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester