Abstract
Chronic intermittent hypoxia (IH) associated with sleep-disordered breathing is an important cause of hypertension, which results from carotid body-mediated activation of the sympathetic nervous system. IH triggers increased levels of reactive oxygen species (ROS) in the carotid body, which induce increased synthesis and stability of hypoxia-inducible factor 1α (HIF-1α) and calpain-dependent degradation of HIF-2α. HIF-1 activates transcription of the Nox2 gene, encoding NADPH oxidase 2, which generates superoxide. Loss of HIF-2 activity leads to decreased transcription of the Sod2 gene, encoding manganese superoxide dismutase, which converts superoxide to hydrogen peroxide. Thus, IH disrupts the balance between HIF-1-dependent pro-oxidant and HIF-2-dependent anti-oxidant activities, and this loss of redox homeostasis underlies the pathogenesis of autonomic morbidities associated with IH.
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Acknowledgements
Research from authors’ laboratories was supported by contracts/grants HHS-N268201000032C, PO1-HL65608, P20-GM78494, RO1-HL55338, U54-CA143868 (G.L.S.) and HL-76537, HL-90554, and HL-86493 (N.R.P) from the National Institutes of Health.
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Semenza, G.L., Prabhakar, N.R. (2012). The Role of Hypoxia-Inducible Factors in Oxygen Sensing by the Carotid Body. In: Nurse, C., Gonzalez, C., Peers, C., Prabhakar, N. (eds) Arterial Chemoreception. Advances in Experimental Medicine and Biology, vol 758. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4584-1_1
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