Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans.
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.
Pialoux
Vincent
V
Departments of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Hanly
Patrick J
PJ
Foster
Glen E
GE
Brugniaux
Julien V
JV
Beaudin
Andrew E
AE
Hartmann
Sara E
SE
Pun
Matiram
M
Duggan
Cailean T
CT
Poulin
Marc J
MJ
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
D017382:Reactive Oxygen Species