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The mechanism(s) underlying these responses are largely unknown. We hypothesized that attenuated carotid body (CB) sensitivity to hypoxia and hypercapnia contributes to the near absence of ventilatory responses to hypoxia and CO<jats:sub>2<\/jats:sub> in NMRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured ex vivo CB sensory nerve activity, phrenic nerve activity (an estimation of ventilation), and blood gases in urethane\u2010anesthetized NMRs and C57BL\/6 mice breathing normoxic, hypoxic, or hypercapnic gases. CB morphology, carbon monoxide, and H<jats:sub>2<\/jats:sub>S levels were also determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Relative to mice, NMRs had blunted CB and HVR. Morphologically, NMRs have larger CBs, which contained more glomus cells than in mice. Furthermore, NMR glomus cells form a dispersed pattern compared to a clustered pattern in mice. Hemeoxygenase (HO)\u20101 mRNA was elevated in NMR CBs, and an HO inhibitor increased CB sensitivity to hypoxia in NMRs. This increase was blocked by an H<jats:sub>2<\/jats:sub>S synthesis inhibitor, suggesting that interrupted gas messenger signaling contributes to the blunted CB responses and HVR in NMRs. Regarding hypercapnia, CB and ventilatory responses to CO<jats:sub>2<\/jats:sub> in NMRs were larger than in mice. Carbonic anhydrase (CA)\u20102 mRNA is elevated in NMR CBs, and a CA inhibitor blocked the augmented CB response to CO<jats:sub>2<\/jats:sub> in NMRs, indicating CA activity regulates augmented CB response to CO<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Consistent with our hypothesis, impaired CB responses to hypoxia contribute in part to the blunted HVR in NMRs. Conversely, the HCVR and CB are more sensitive to CO<jats:sub>2<\/jats:sub> in NMRs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13851","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T08:09:25Z","timestamp":1656317365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Carotid body responses to <scp>O<sub>2<\/sub><\/scp> and <scp>CO<sub>2<\/sub><\/scp> in hypoxia\u2010tolerant naked mole rats"],"prefix":"10.1111","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8302-5198","authenticated-orcid":false,"given":"Ying\u2010Jie","family":"Peng","sequence":"first","affiliation":[{"name":"Institute for Integrative Physiology and Center for Systems Biology of O<sub>2<\/sub> Sensing University of Chicago  Chicago Illinois 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