The role of hypoxia-inducible factors in carotid body (patho) physiology

Gregg L. Semenza, Nanduri R. Prabhakar

Research output: Contribution to journalReview articlepeer-review


Hypoxia-inducible factors mediate adaptive responses to reduced O2 availability. In patients with obstructive sleep apnoea, repeated episodes of hypoxaemia and reoxygenation (intermittent hypoxia) are sensed by the carotid body (CB). The ensuing CB chemosensory reflex activates the sympathetic nervous system and increased secretion of catecholamines by the adrenal medulla, resulting in hypertension and breathing abnormalities. In the CB, intermittent hypoxia induces the formation of reactive oxygen species (ROS) and increased intracellular Ca2+ levels, which drive increased expression of hypoxia-inducible factor (HIF) 1α and a decrease in the levels of HIF-2α. Intermittent hypoxia increases HIF-1α-dependent expression of Nox2, encoding the pro-oxidant enzyme NADPH oxidase 2, and decreased HIF-2α-dependent expression of Sod2, encoding the anti-oxidant enzyme superoxide dismutase 2. These changes in gene expression drive persistently elevated ROS levels in the CB, brainstem, and adrenal medulla that are required for the development of hypertension and breathing abnormalities. The ROS generated by dysregulated HIF activity in the CB results in oxidation and inhibition of haem oxygenase 2, and the resulting reduction in the levels of carbon monoxide leads to increased hydrogen sulfide production, triggering glomus cell depolarization. Thus, the pathophysiology of obstructive sleep apnoea involves the dysregulation of O2-regulated transcription factors, gasotransmitters, and sympathetic outflow that affects blood pressure and breathing. (Figure presented.).

Original languageEnglish (US)
Pages (from-to)2977-2983
Number of pages7
JournalJournal of Physiology
Issue number15
StatePublished - Aug 1 2018


  • HIF-1
  • HIF-2
  • NADPH oxidase
  • Redox State
  • Superoxide dismutase
  • sleep apnea

ASJC Scopus subject areas

  • Physiology


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