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These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species\u2013dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.<\/jats:p>","DOI":"10.1126\/sciadv.abm1444","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T17:58:19Z","timestamp":1648231099000},"source":"Crossref","is-referenced-by-count":25,"title":["Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-3588","authenticated-orcid":true,"given":"Nicole O.","family":"Barioni","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children\u2019s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, 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