title: Testosterone and resistance training effects on muscle nitric oxide synthase isoforms in COPD men.
abstract: BACKGROUND
  Skeletal muscle dysfunction contributes to exercise limitation in COPD. The role of the nitric oxide synthase (NOS) system in muscle dysfunction is ill defined. Reduced levels of endothelial NOS (eNOS) and elevated levels of inducible NOS (iNOS) in the skeletal muscle of COPD patients have been recently reported. We hypothesized that resistance exercise training (R) and/or testosterone supplementation (T) would alter the transcription and expression of the NOS isoenzymes in COPD skeletal muscle.
  
  
  METHODS
  Vastus lateralis biopsies were obtained before and after a 10-week intervention in 40 men with severe COPD(age 67.7 ± 8.3, FEV(1) 41.4 ± 12.6% predicted): placebo + no training (P) (n = 11), placebo + resistance training (PR) (n = 8), testosterone + no training (T) (n = 11) and testosterone + resistance training (TR) (n = 10) groups. eNOS, nNOS and iNOS mRNA and protein levels were measured in each sample. mRNA and protein levels were measured using real-time PCR and enzyme-linked immunosorbant assay, respectively.
  
  
  RESULTS
  eNOS mRNA increased in the TR group compared to P and T groups (P < 0.001). eNOS protein was increased in TR and T groups after intervention (P < 0.05) but not in the PR group. nNOS protein increased in the PR, T, and TR groups (P < 0.05). iNOS protein decreased only in the TR group (P = 0.01).
  
  
  CONCLUSIONS
  Resistance training and testosterone supplementation increased eNOS and nNOS proteins and decreased iNOS protein in the skeletal muscles of men with COPD. These changes in NO system might explain some of the favorable effects of these therapies.
authors.affiliation: Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. b.chavoshan@ucla.edu
authors.forename: Bahman
authors.initials: B
authors.lastname: Chavoshan
authors.forename: Mario
authors.initials: M
authors.lastname: Fournier
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lewis
authors.forename: Janos
authors.initials: J
authors.lastname: Porszasz
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Storer
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Da
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rambod
authors.forename: Richard
authors.initials: R
authors.lastname: Casaburi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055070:Resistance Training / Q000379:methods; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D013739:Testosterone; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III