Respiratory Plasticity in the Behaving Rat Following Chronic Intermittent Hypoxia

  • Deirdre Edge
  • J. Richard Skelly
  • Aidan Bradford
  • Ken D. O’Halloran
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)


Chronic intermittent hypoxia (CIH), a feature of obstructive sleep apnoea (OSA) has been shown to have myriad effects on the respiratory control system. The effects on breathing are of great clinical significance for the sleep apnoea patient. We sought to determine the effect of CIH on normoxic ventilation. Both male and female adult Wistar rats were studied due to the evident sex difference in the prevalence of OSA. A role for oxidative stress in respiratory modifications was also explored. Adult male (n = 30) and female (n = 16) rats were exposed to alternating periods of N2 and O2 for 90 s each, bringing the ambient oxygen concentration to 5% at nadir (CIH) group. Sham groups were subject to cycles of air/air under identical experimental conditions. A subset of male rats (8 controls, 8 CIH) had free access to water containing 1 mM Tempol (SOD-mimetic) at all times. Treatments were carried out for 8 hours a day for 9 days. Following treatment, normoxic ventilation was assessed by whole body plethysmography in sleeping animals. Baseline normoxic ventilation was increased in both male and female treated rats but this did not achieve statistical significance. However, ventilatory drive (VT/Ti) was significantly increased in male rats. Chronic treatment with Tempol abolished this effect. Conversely, CIH had no significant effect on VT/Ti in female rats. Our results indicate subtle effects of intermittent hypoxia on breathing in conscious behaving rats. We speculate the increased ventilatory drive following CIH represents a form a neural plasticity - a ROS dependent phenomenon – with sexual dimorphism.


Obstructive Sleep Apnoea Intermittent Hypoxia Ventilatory Response Chronic Intermittent Hypoxia Ventilatory Drive 
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  1. Behan, M., Zabka, A.G. et al. (2002) Age and gender effects on serotonin-dependent plasticity in respiratory motor control. Respir. Physiol. Neurobiol. 131(1–2), 65–77.CrossRefGoogle Scholar
  2. Behan, M., Zabka, A.G. et al. (2003) Sex steroid hormones and the neural control of breathing. Respir. Physiol. Neurobiol. 136(2–3), 249–263.Google Scholar
  3. Bixler, E.O., Vgontzas, A.N. et al. (2001) Prevalence of sleep-disordered breathing in women: effects of gender. Am. J. Respir. Crit. Care Med. 163(3 Pt 1), 608–613.PubMedGoogle Scholar
  4. Lavie, L. (2009) Oxidative stress – a unifying paradigm in obstructive sleep apnea and comorbidities. Prog. Cardiovasc. Dis. 51(4), 303–312.CrossRefPubMedGoogle Scholar
  5. McGuire, M., Zhang, Y. et al. (2003) Chronic intermittent hypoxia enhances ventilatory long-term facilitation in awake rats. J. Appl. Physiol. 95(4), 1499–1508.PubMedGoogle Scholar
  6. Mitchell, G.S., Baker, T.L. et al. (2001) Invited review: Intermittent hypoxia and respiratory plasticity. J. Appl. Physiol. 90(6), 2466–2475.PubMedGoogle Scholar
  7. O'Halloran, K.D., McGuire, M. et al. (2002) Chronic intermittent asphyxia impairs rat upper airway muscle responses to acute hypoxia and asphyxia. Chest 122(1), 269–275.CrossRefPubMedGoogle Scholar
  8. O'Halloran, K.D., McGuire, M., and Bradford, A. (2007) Respiratory plasticity following chronic intermittent hypercapnic hypoxia in conscious rats. The Joint Meeting of the Slovak Physiological Society, 99–103.Google Scholar
  9. Ray, A.D., Magalang, U.J. et al. (2007) Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293(1), R372–378.PubMedGoogle Scholar
  10. Reeves, S.R., and Gozal, D. (2006) Changes in ventilatory adaptations associated with long-term intermittent hypoxia across the age spectrum in the rat. Respir. Physiol. Neurobiol. 150(2–3), 135–143.CrossRefPubMedGoogle Scholar
  11. Rey, S., Valdes, G. et al. (2007) Pathophysiology of obstructive sleep apnea-associated hypertension. Rev. Med. Chil. 135(10), 1333–1342.PubMedGoogle Scholar
  12. Row, B.W. (2007) Intermittent hypoxia and cognitive function: Implications from chronic animal models. Adv. Exp. Med. Biol. 618, 51–67.CrossRefPubMedGoogle Scholar
  13. Veasey, S.C., Zhan, G. et al. (2004) Long-term intermittent hypoxia: reduced excitatory hypoglossal nerve output. Am. J. Respir. Crit. Care Med. 170(6), 665–672.CrossRefPubMedGoogle Scholar
  14. Vinit, S., Lovett-Barr, M.R. et al. (2009) Intermittent hypoxia induces functional recovery following cervical spinal injury . Respir. Physiol. Neurobiol. 169, 210–217.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Deirdre Edge
    • 1
  • J. Richard Skelly
    • 1
  • Aidan Bradford
    • 2
  • Ken D. O’Halloran
    • 1
  1. 1.School of Medicine and Medical SciencesUniversity College DublinDublin 4Ireland
  2. 2.Department of Physiology and Medical PhysicsRoyal College of Surgeons in Ireland, St Stephens GreenDublin 2Ireland

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