during sleep, causing concomitant episodes of systemic hypoxia and associated cardiovascular and
metabolic pathologies. The mechanisms generating these pathologies are controversial. Because recurrent
hypoxia is the element of inadequate respiration that leads to the pathology, experimental models of OSAS
consist in the exposure of the animals to intermittent hypoxia (IH) by cycling O2 percentages in their
habitats. A proposed mechanism linking the IH of OSAS to pathologies is the increased production of
reactive oxygen species (ROS). However, it has been argued that many patients seem to lack oxidative
stress and that, to augment ROS in IH animals, intense hypoxia, seldom encountered in patients, has to be
applied. To solve the controversy, we have exposed rats to two intensities of IH (cycles of 10 or 5% O2, 40 s,
and then 21% O2, 80 s; 8 h/day, 15 days). We then measured reduced and oxidized glutathione and lipid
peroxide levels, aconitase and fumarase activities, and ROS-disposal enzyme activity in liver, brain, and
lung. Liver levels of nuclear NF-κB-p65 and plasma C-reactive protein (CRP), as well as lipid levels, were
also assessed. Lowest hemoglobin saturations were 91.770.8 and 73.571.4%. IH caused tissue-specific
oxidative stress related to hypoxic intensity. Nuclear NF-κB-p65 and lipid content in the liver and CRP in
the plasma all increased with IH intensity, as did both plasma triglycerides and cholesterol. We conclude
that IH, even of moderate intensity, causes oxidative stress probably related to the pathologies encountered
in OSAS patients.
