Intermittent hypoxia has organ-specific effects on oxidative stress

Jonathan Jun, Vladimir Savransky, Ashika Nanayakkara, Shannon Bevans, Jianguo Li, Philip L. Smith, Vsevolod Y. Polotsky

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Obstructive sleep apnea is characterized by upper airway collapse, leading to intermittent hypoxia (IH). It has been postulated that IH-induced oxidative stress may contribute to several chronic diseases associated with obstructive sleep apnea. We hypothesize that IH induces systemic oxidative stress by upregulating NADPH oxidase, a superoxide-generating enzyme. NADPH oxidase is regulated by a cytosolic p47phox subunit, which becomes phosphorylated during enzyme activation. Male C57BL/6J mice were exposed to IH with an inspired O2 fraction nadir of 5% 60 times/h during the 12-h light phase (9 AM-9 PM) for 1 or 4 wk. In the aorta and heart, IH did not affect lipid peroxidation [malondialdehyde (MDA) level], nitrotyrosine level, or p47phox expression and phosphorylation. In contrast, in the liver, exposure to IH for 1 wk resulted in a trend to an increase in MDA levels, whereas IH for 4 wk resulted in a 38% increase in MDA levels accompanied by upregulation of p47phox expression and phosphorylation. Administration of an NADPH oxidase inhibitor, apocynin, during IH exposure attenuated IH-induced increases in hepatic MDA. In p47phox-deficient mice, MDA levels were higher at baseline and, unexpectedly, decreased during IH. In conclusion, oxidative stress levels and pathways under IH conditions are organ and duration specific.

Original languageEnglish (US)
Pages (from-to)R1274-R1281
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4
StatePublished - Oct 2008


  • NADPH oxidase
  • Obstructive sleep apnea

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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