Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea

Gregg L. Semenza, Nanduri R. Prabhakar

Research output: Contribution to journalReview articlepeer-review

Abstract

Semenza GL, Prabhakar NR. Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea. J Appl Physiol 119: 1152-1156, 2015. First published May 7, 2015; doi:10.1152/japplphysiol.00162.2015.-Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O2-sensing glomus cells of the carotid body. CIH generates increased reactive oxygen species (ROS) that trigger a feedforward mechanism in which increased intracellular calcium levels ([Ca2+]i) trigger increased HIF-1α synthesis and increased HIF-2α degradation. As a result, the normal homeostatic balance between HIF-1α-dependent prooxidant and HIF-2α-dependent antioxidant enzymes is disrupted, leading to further increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarii, from which the information is relayed via interneurons to the rostral ventrolateral medulla in the brain stem, which sends sympathetic neurons to the adrenal medulla to stimulate the release of epinephrine and norepinephrine, catecholamines that increase blood pressure. At each synapse, neurotransmitters trigger increased [Ca2+]i, HIF-1α:HIF-2α, and Nox2:Sod2 activity that generates increased ROS levels. These responses are not observed in other regions of the brain stem that do not receive input from the carotid body or signal to the sympathetic nervous system. Thus sympathetic nervous system homeostasis is dependent on a balance between HIF-1α and HIF-2α, disruption of which results in hypertension in OSA patients.

Original languageEnglish (US)
Pages (from-to)1152-1156
Number of pages5
JournalJournal of applied physiology
Volume119
Issue number10
DOIs
StatePublished - Nov 15 2015

Keywords

  • Hypoxia-inducible factors
  • NADPH oxidase
  • Oxidative stress
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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