title: Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes.
abstract: OBJECTIVE
  We sought to determine whether the benefit of training for vasodilation in the skeletal muscle vasculature of patients with chronic heart failure (CHF) is likely to be caused at the molecular level primarily by increased nitric oxide (NO) production or decreased inactivation of NO.
  
  
  BACKGROUND
  Physical training reverses endothelium dysfunction in patients with CHF, mediated by increased NO bioactivity. Some animal studies support a mechanism whereby training results in increased vascular NO levels by sustained transcriptional activation of the endothelial NO synthase (eNOS) gene, presumably due to shear stress. The mechanism has not been addressed in patients with CHF.
  
  
  METHODS
  The steady state transcript levels for eNOS and two other shear stress regulated genes (angiotensin-converting enzyme [ACE] and prostacyclin synthase [PGI2S]) were measured in samples of skeletal muscle from patients with CHF before and after 12 weeks of training. Transcript levels were measured in the same samples for two genes encoding antioxidant enzymes, copper zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px). Untrained patients served as controls.
  
  
  RESULTS
  As expected, training significantly enhanced peak oxygen uptake in the patients with CHF. Training did not increase steady-state transcript levels for eNOS, ACE or PGI2S. In striking contrast, training increased the expression of the antioxidative enzyme genes by approximately 100%.
  
  
  CONCLUSIONS
  Our results do not support a model of benefit from training by increased eNOS expression. However, the data are entirely consistent with the alternative hypothesis, that reduced oxidative stress may account for the increase in vascular NO-mediated vasodilation. Insight into the mechanism may be relevant when considering therapies for exercise-intolerant patients with CHF.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Ennezat
authors.forename: S L
authors.initials: SL
authors.lastname: Malendowicz
authors.forename: M
authors.initials: M
authors.lastname: Testa
authors.forename: P C
authors.initials: PC
authors.lastname: Colombo
authors.forename: A
authors.initials: A
authors.lastname: Cohen-Solal
authors.forename: T
authors.initials: T
authors.lastname: Evans
authors.forename: T H
authors.initials: TH
authors.lastname: LeJemtel
mesh_terms: D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005081:Exercise Therapy; D006333:Heart Failure / Q000503:physiopathology* / Q000534:rehabilitation*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014664:Vasodilation / Q000502:physiology
chemical_list: D003577:Cytochrome P-450 Enzyme System; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase