{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:38:07Z","timestamp":1790642287155,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["PO1\u2010HL\u201090554"],"award-info":[{"award-number":["PO1\u2010HL\u201090554"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxia\u2010inducible factors mediate adaptive responses to reduced O<jats:sub>2<\/jats:sub> 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 Ca<jats:sup>2+<\/jats:sup> levels, which drive increased expression of hypoxia\u2010inducible factor (HIF) 1\u03b1 and a decrease in the levels of HIF\u20102\u03b1.\u00a0 Intermittent hypoxia increases HIF\u20101\u03b1\u2010dependent expression of <jats:italic>Nox2<\/jats:italic>, encoding the pro\u2010oxidant enzyme NADPH oxidase 2, and decreased HIF\u20102\u03b1\u2010dependent expression of <jats:italic>Sod2<\/jats:italic>, encoding the anti\u2010oxidant 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 O<jats:sub>2<\/jats:sub>\u2010regulated transcription factors, gasotransmitters, and sympathetic outflow that affects blood pressure and breathing.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp12824-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp275696","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T11:52:59Z","timestamp":1516708379000},"page":"2977-2983","source":"Crossref","is-referenced-by-count":83,"title":["The role of hypoxia\u2010inducible factors in carotid body (patho) 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