{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:38:51Z","timestamp":1792525131362,"version":"4.5.0"},"reference-count":79,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01-HL144454"],"award-info":[{"award-number":["P01-HL144454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:p>\n                    Carotid bodies (CBs) sense arterial blood O\n                    <jats:sub>2<\/jats:sub>\n                    levels. Hypoxemia activates the carotid sinus nerve (CSN) afferent activity to elicit cardiorespiratory reflexes to maintain tissue oxygenation. This brief review presents emerging evidence suggesting that CBs use distinct O\n                    <jats:sub>2<\/jats:sub>\n                    -sensing mechanisms depending on the severity of hypoxia. During physiologically relevant moderate hypoxia (Po\n                    <jats:sub>2<\/jats:sub>\n                    \u223c40 mmHg), glomus cells use the heme oxygenase-2 (HO-2)\/carbon monoxide (CO)\/cystathionine-\u03b3-lyase (CSE)\/hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) signaling to stimulate CSN activity and the breathing response to hypoxia. Basal CO restrains CSN activity during normoxia, whereas hypoxia reduces CO and stimulates CSN activity through H\n                    <jats:sub>2<\/jats:sub>\n                    S. Olfactory receptor 78 (Olfr78) is required for H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated CSN activation. CO-H\n                    <jats:sub>2<\/jats:sub>\n                    S pathway contributes to cardiorespiratory adaptations to sustained hypoxia and to the pathophysiology of diseases characterized by carotid body (CB) hyperactivity. In contrast, glomus cells respond to severe hypoxia (Po\n                    <jats:sub>2<\/jats:sub>\n                    \u223c5\u201315 mmHg) through mitochondrial complex I (NDUFS2) and complex III. Thus, CBs appear to use severity-dependent hypoxic sensing mechanisms, wherein moderate hypoxia engages the CO-H\n                    <jats:sub>2<\/jats:sub>\n                    S pathway to activate CSN activity and drive homeostatic cardiorespiratory responses. Severe hypoxia primarily alters mitochondrial function and glomus cell metabolism. The physiological relevance of severe hypoxia remains uncertain, because severe low O\n                    <jats:sub>2<\/jats:sub>\n                    levels suppress both CB and CSN activity and ventilation.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.90003.2026","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:32:14Z","timestamp":1790789534000},"page":"L522-L529","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxic intensity reveals distinct carotid body O\n                    <sub>2<\/sub>\n                    -sensing mechanisms"],"prefix":"10.1152","volume":"331","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-1380","authenticated-orcid":false,"given":"Nanduri R.","family":"Prabhakar","sequence":"first","affiliation":[{"name":"The University of Chicago","place":["United 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