title: Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans.
abstract: BACKGROUND
  Periodic occlusion of the upper airway in patients with obstructive sleep apnea leads to chronic intermittent hypoxia, which increases the acute hypoxic ventilatory response (AHVR). Animal studies suggest that oxidative stress may modulate AHVR by increasing carotid body sensitivity to hypoxia. This has not been shown in humans.
  
  
  OBJECTIVE
  To determine whether 4 days of exposure to chronic intermittent hypoxia increases AHVR and oxidative stress and to determine the strength of the association between oxidative stress and AHVR.
  
  
  METHODS
  After two normoxic control days (Day -4 and Day 0), 10 young healthy men were exposed awake to 4 days (Days 1-4) of intermittent hypoxia for 6 hours per day.
  
  
  RESULTS
  AHVR, assessed using an isocapnic hypoxia protocol, was determined as the slope of the linear regression between ventilation and oxygen desaturation. Oxidative stress was evaluated by measuring plasma DNA, lipid and protein oxidation, uric acid and antioxidant status by measuring alpha-tocopherol, total vitamin C, and antioxidant enzymatic activities. Between baseline and Day 4, there were significant increases in AHVR, DNA oxidation, uric acid, and vitamin C, whereas antioxidant enzymatic activities and alpha-tocopherol were unchanged. There were strong correlations between the changes in AHVR and DNA oxidation (r = 0.88; P = 0.002).
  
  
  CONCLUSIONS
  Chronic intermittent hypoxia increases oxidative stress by increasing production of reactive oxygen species without a compensatory increase in antioxidant activity. This human study shows that reactive oxygen species overproduction modulates increased AHVR. These mechanisms may be responsible for increased AHVR in patients with obstructive sleep apnea.
authors.affiliation: Departments of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanly
authors.forename: Glen E
authors.initials: GE
authors.lastname: Foster
authors.forename: Julien V
authors.initials: JV
authors.lastname: Brugniaux
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Beaudin
authors.forename: Sara E
authors.initials: SE
authors.lastname: Hartmann
authors.forename: Matiram
authors.initials: M
authors.lastname: Pun
authors.forename: Cailean T
authors.initials: CT
authors.lastname: Duggan
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
mesh_terms: D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012129:Respiratory Function Tests; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology
chemical_list: D017382:Reactive Oxygen Species