ROS signaling in systemic and cellular responses to chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) is a common and life-threatening condition that occurs in many different diseases, including sleep-disordered breathing manifested as recurrent apneas. Reactive oxygen species (ROS) have been identified as one of the causative factors in a variety of morbidities. The purpose of this article is to present a brief overview of recent studies implicating a critical role of ROS in evoking phenotypic adverse effects in experimental models of CIH and in patients with recurrent apneas. In experimental models, CIH activates ROS signaling that contributes to several systemic and cellular responses that include (a) altered carotid body function, the primary chemoreceptor for sensing changes in arterial blood O2; (b) elevated blood pressures; (c) enhanced release of transmitters and neurotrophic factors; (d) altered sleep and cognitive behaviors; and (e) activation of second-messenger pathways and transcriptional factors. Considerable evidence indicates elevated ROS levels in patients experiencing CIH as a consequence of recurrent apneas. Antioxidants not only prevent many of the CIH-evoked physiologic and cellular responses in experimental settings, but more important, they also offer protection against certain phenotypic adverse effects in patients with recurrent apneas, suggesting their potential therapeutic value in alleviating certain morbidities associated with recurrent apneas.