Chronic Intermittent Hypoxia Increases Apnoea Index in Sleeping Rats
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Intermittent hypoxia (IH) is the dominant feature of sleep-disordered breathing which is very common. It is recognized that IH elicits plasticity in the respiratory control system. Recently it was reported in humans that IH destabilizes breathing during sleep increasing the susceptibility to apnoea. Many forms of respiratory plasticity are dependent upon reactive oxygen species (ROS), and NADPH oxidase has been identified as an important source of ROS necessary for IH-induced plasticity. In the present study, we sought to examine the effects of chronic IH (CIH) on the propensity for spontaneous apnoea during sleep. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5% O2 at nadir; SaO2 ∼ 80%) per hour, 8 h a day for 7 consecutive days (CIH group, N = 6). The sham group (N = 6) were subject to alternating cycles of air under identical experimental conditions in parallel. Two additional groups of CIH-treated rats were given either the superoxide dismutase mimetic – tempol (1 mM, N = 8), or the NAPDH oxidase inhibitor – apocynin (2 mM, N = 8) in their drinking water throughout the study. Following gas exposures, breathing during sleep was assessed in unrestrained animals using the technique of whole-body plethysmography. CIH significantly increased apnoea index during sleep (4.7 ± 0.8 vs. 11.3 ± 1.6 events/h; mean ± SEM, sham vs. CIH, Student’s t test, p = 0.0035). Apnoea duration was unaffected by CIH treatment. The CIH-induced increase in the occurrence of apnoea was completely reversed by antioxidant supplementation (4.9 ± 0.9 events/h for CIH + tempol and 5.6 ± 0.9 events/h for CIH + apocynin). CIH-induced increase in the propensity for apnoea may have clinical relevance and may explain the phenomenon of ‘complex’ apnoea in sleep apnoea patients. Our results suggest that oxidative stress is implicated in CIH-induced respiratory disturbance during sleep. We conclude that antioxidants may be a realistic adjunct therapy in the treatment of sleep-disordered breathing.
KeywordsChronic intermittent hypoxia Sleep disordered breathing Animal model Plasticity Apnoea index Reactive oxygen species Oxidative stress Respiratory neurons NADPH-oxidase Antioxidants
Supported by the Health Research Board, Ireland (RP/2007/29). DE is enrolled in the School of Medicine and Medical Science Translational Medicine PhD training programme.
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