Oxidative stress impairs upper airway muscle endurance in an animal model of sleep-disordered breathing.
Obstructive sleep apnoea is characterised by intermittent hypoxia due to recurrent obstructions of the pharyngeal airway during sleep. We have shown that chronic intermittent hypoxia impairs respiratory muscle function and CNS control of upper airway patency. In this study, we tested the hypothesis that disruption of an endogenous antioxidant defence system exacerbates the effects of intermittent hypoxia on upper airway muscle contractile function. Thirty-two male Wistar rats were placed in restrainers with their heads in hoods in which the ambient oxygen concentration could be modified by controlling the gas supply to the hoods. Sixteen rats were exposed to alternating equal periods of hypoxia and normoxia, twice per minute, 8 hours per day for 1 week. The remaining 16 animals were exposed to normoxia continuously under identical experimental conditions. In both groups, half the animals received daily injections of buthionine sulfoxamine (BSO), an inhibitor of the rate-limiting enzyme in glutathione synthesis. The other half received daily vehicle injections. At the end of the 1-week treatment period, the sternohyoid muscles were removed and fatigue characteristics were determined in vitro. Intermittent hypoxia was associated with a decrease in sternohyoid muscle endurance, an effect that was exacerbated by treatment with BSO. In separate experiments, daily treatment with the antioxidant N-acetyl cysteine blocked the deleterious effects of intermittent hypoxia on respiratory muscle function. We suggest that oxidative stress contributes to impaired upper airway muscle endurance in our animal model and that endogenous glutathione may be especially important in limiting free radical-induced muscle dysfunction. Our results may have particular relevance to respiratory disorders associated with recurrent hypoxia, such as the sleep apnoea/hypopnoea syndrome.
Dunleavy
Mark
M
Royal College of Surgeons in Ireland, Department of Physiology and Medical Physics. mdunleavy@rcsi.ie
Bradford
Aidan
A
O'Halloran
Ken D
KD
D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D018763:Muscle Fatigue / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012120:Respiration Disorders / Q000209:etiology* / Q000503:physiopathology; D012132:Respiratory Muscles / Q000503:physiopathology*; D012893:Sleep Wake Disorders / Q000503:physiopathology*