{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:11:28Z","timestamp":1792620688339,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"\n Key points<\/jats:title>\n \n \n \n \n The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO\n 2<\/jats:sub>\n \u2013[H\n +<\/jats:sup>\n ] washout\u2010induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO\n 2<\/jats:sub>\n affinity for haemoglobin.\n <\/jats:p>\n <\/jats:list-item>\n \n Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation\/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation.<\/jats:p>\n <\/jats:list-item>\n \n We then quantified ventilation, cerebral perfusion\/metabolism, arterial\/internal jugular vein blood gases and oxidant\/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production\/accumulation contributes to the hyperoxia\u2010induced hyperventilation in humans.<\/jats:p>\n <\/jats:list-item>\n \n Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production\/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion.<\/jats:p>\n <\/jats:list-item>\n \n \n Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production\/accumulation and reduced brain CO\n 2<\/jats:sub>\n \u2013[H\n +<\/jats:sup>\n ] washout.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n The hypothetical mechanism for the increase in ventilation (\n \n ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO\n 2<\/jats:sub>\n \u2013[H\n +<\/jats:sup>\n ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production\/accumulation may increase the sensitivity to CO\n 2<\/jats:sub>\n or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX\u2010evoked increase in\n \n , 10 healthy men (24\u00a0\u00b1\u00a04 years) underwent 10\u00a0min trials of HX under saline and ascorbic acid infusion.\n \n , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO\n 2<\/jats:sub>\n ) and CO\n 2<\/jats:sub>\n (PCO\n 2<\/jats:sub>\n ), pH, oxidant (8\u2010isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8\u2010isoprostane, and unchanged PijvCO\n 2<\/jats:sub>\n and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8\u2010isoprostane and attenuated both the reduction in CBF and the HX\u2010induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO\n 2<\/jats:sub>\n and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans\u2010cerebral exchanges for PCO\n 2<\/jats:sub>\n and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO\n 2<\/jats:sub>\n , which, in turn, seems to be evoked by the excessive ROS production\/accumulation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp281635","type":"journal-article","created":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T04:24:54Z","timestamp":1625891094000},"page":"3993-4007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-2656","authenticated-orcid":false,"given":"Igor A.","family":"Fernandes","sequence":"first","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7377-9348","authenticated-orcid":false,"given":"Jo\u00e3o D.","family":"Mattos","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9526-0937","authenticated-orcid":false,"given":"Monique O.","family":"Campos","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-3139","authenticated-orcid":false,"given":"Marcos P.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-9910","authenticated-orcid":false,"given":"Daniel E.","family":"Mansur","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-7343","authenticated-orcid":false,"given":"Helena M.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-1616","authenticated-orcid":false,"given":"Vinicius P.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2261-8501","authenticated-orcid":false,"given":"Thiago","family":"Alvares","sequence":"additional","affiliation":[{"name":"Federal University of Rio de Janeiro Maca\u00e9 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels H.","family":"Secher","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Rigshospitalet, Institute for Clinical Medicine University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-2886","authenticated-orcid":false,"given":"Antonio C.L.","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Sciences Fluminense Federal University Niter\u00f3i 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