title: Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling.
abstract: BACKGROUND
  Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function.
  
  
  METHODS
  Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters.
  
  
  RESULTS
  Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular-arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs.
  Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function.
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: jmaga@fade.up.pt.
authors.forename: J
authors.initials: J
authors.lastname: Magalhães
authors.forename: I
authors.initials: I
authors.lastname: Falcão-Pires
authors.forename: I O
authors.initials: IO
authors.lastname: Gonçalves
authors.forename: J
authors.initials: J
authors.lastname: Lumini-Oliveira
authors.forename: I
authors.initials: I
authors.lastname: Marques-Aleixo
authors.forename: E
authors.initials: E
authors.lastname: Dos Passos
authors.forename: S
authors.initials: S
authors.lastname: Rocha-Rodrigues
authors.forename: N G
authors.initials: NG
authors.lastname: Machado
authors.forename: A C
authors.initials: AC
authors.lastname: Moreira
authors.forename: D
authors.initials: D
authors.lastname: Miranda-Silva
authors.forename: C
authors.initials: C
authors.lastname: Moura
authors.forename: A F
authors.initials: AF
authors.lastname: Leite-Moreira
authors.forename: P J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: J R
authors.initials: JR
authors.lastname: Torrella
authors.forename: A
authors.initials: A
authors.lastname: Ascensão
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000531:Altitude; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D059467:Transcriptome
keywords: Altitude; Bioenergetics; Cardioprotection; Physical exercise