title: Oxidative stress in the systemic and cellular responses to intermittent hypoxia.
abstract: Patients with chronic intermittent hypoxia (IH) caused by recurrent apneas have a greatly increased risk for developing hypertension, myocardial infarctions, and stroke. The purpose of this article is to highlight some of the recent studies focusing on the mechanisms associated with systemic and cellular effects of IH in experimental animals and cell culture models. Rats exposed to chronic IH exhibited elevated blood pressures and increased sympathetic nerve activity, partly due to enhanced reflexes arising from carotid bodies. Direct recordings of the carotid body sensory activity showed that chronic IH selectively augmented hypoxic sensitivity, and induced a novel form of functional plasticity manifested as sensory long-term facilitation. In cell culture models, prior exposure to IH resulted in facilitation of hypoxia-induced transmitter release and activation of several protein kinases. IH caused activation of c-Fos and activator protein-1 (AP-1) transcription factor and tyrosine hydroxylase, an AP-regulated downstream gene. For a given duration and intensity of hypoxia, IH was more potent and caused longer-lasting activation than continuous hypoxia. Scavengers of reactive oxygen species (ROS) prevented IH-induced systemic and cellular responses. Inhibition of complex I of the mitochondrial electron transport chain appears to be one of the sources for IH-induced generation of ROS. The persistent oxidative stress may contribute to the progression of morbidity associated with chronic IH caused by recurrent apneas, and antioxidants might be of considerable therapeutic value in preventing the progression of disease associated with chronic IH.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA. nrp@po.cwru.edu
authors.forename: Nanduri R
authors.initials: NR
authors.lastname: Prabhakar
authors.forename: Ganesh K
authors.initials: GK
authors.lastname: Kumar
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*