{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:43:29Z","timestamp":1791272609602,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,11,24]],"date-time":"2006-11-24T00:00:00Z","timestamp":1164326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>Chronic intermittent hypoxia (CIH) occurs in patients with sleep apnoea and has adverse effects on multiple physiological functions. Previous studies have shown that reflexes arising from carotid bodies mediate CIH\u2010evoked cardio\u2010respiratory responses, and reactive oxygen species (ROS) play important roles in eliciting systemic responses to CIH. Very little is known about the molecular mechanisms underlying CIH. The transcriptional activator hypoxia\u2010inducible factor\u20101 (HIF\u20101) mediates a broad range of cellular and systemic responses to hypoxia, and HIF\u20101 is activated in cell cultures exposed to IH. In the present study we examined whether CIH activates HIF\u20101 and if so whether it contributes to cardio\u2010respiratory responses and ROS generation in mice. Experiments were performed on male littermate wild\u2010type (WT) and heterozygous (HET) mice partially deficient in HIF\u20101\u03b1, the O<jats:sub>2<\/jats:sub> regulated subunit of the HIF\u20101 complex. Both groups of mice were exposed to either 10 days of CIH (15 s of hypoxia followed by 5 min of normoxia, 9 episodes h<jats:sup>\u22121<\/jats:sup>, 8 h day<jats:sup>\u22121<\/jats:sup>) or to 10 days of 21% O<jats:sub>2<\/jats:sub> (controls). Carotid body response to hypoxia was augmented, and acute intermittent hypoxia (AIH) induced sensory long\u2010term facilitation (sLTF) of the chemoreceptor activity in CIH\u2010exposed WT mice. In striking contrast, hypoxic sensory response was unaffected and AIH was ineffective in eliciting sLTF in CIH\u2010exposed HET mice. Analysis of cardio\u2010respiratory responses in CIH\u2010exposed WT mice revealed augmented hypoxic ventilatory response, LTF of breathing, elevated blood pressures and increased plasma noradrenaline. In striking contrast these responses were either absent or attenuated in HET mice exposed to CIH. In CIH\u2010exposed WT mice, ROS were elevated and this response was absent in HET mice. Manganese (III) tetrakis(1\u2010methyl\u20104\u2010pyridyl) porphyrin pentachloride, a potent scavenger of superoxide, not only prevented CIH\u2010induced increases in ROS but also CIH\u2010evoked HIF\u20101\u03b1 up\u2010regulation in WT mice. These results indicate that: (a) HIF\u20101 activation is critical for eliciting CIH\u2010induced carotid body\u2010mediated cardio\u2010respiratory responses; (b) CIH increases ROS; and (c) the effects of CIH involve complex positive interactions between HIF\u20101 and ROS.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.114033","type":"journal-article","created":{"date-parts":[[2006,9,15]],"date-time":"2006-09-15T00:32:36Z","timestamp":1158280356000},"page":"705-716","source":"Crossref","is-referenced-by-count":334,"title":["Heterozygous HIF\u20101\u03b1 deficiency impairs carotid body\u2010mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia"],"prefix":"10.1113","volume":"577","author":[{"given":"Ying\u2010Jie","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deviprasadh","family":"Ramakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh D.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bosch\u2010Marce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh K.","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg L.","family":"Semenza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanduri R.","family":"Prabhakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO;2-8"},{"key":"e_1_2_5_3_1","first-page":"157","article-title":"Comparative stability of physiological parameters during sustained anesthesia in rats","volume":"28","author":"Buelke\u2010Sam J","year":"1978","journal-title":"Laboratory Anim Sci"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.89.5.1937"},{"key":"e_1_2_5_5_1","first-page":"405","volume-title":"Sleep and Breathing","author":"Cistulli PA","year":"1994"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1962.42.3.335"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.7.2104126"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.5.1978"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1992.262.6.R1040"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.2.521"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.001"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2005.12.003"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.2.149"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01083.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2005.03.010"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00879.2003"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022634199"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.273bi.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.112524"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2958"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00523.2002"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.9.1183"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1734109100"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00613.2002"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00820.2003"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02988.x"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.072033"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5510"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3062005re12"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5912"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.058503"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407706200"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000601)88:11<2606::AID-CNCR25>3.0.CO;2-W"},{"key":"e_1_2_5_34_1","first-page":"5830","article-title":"Overexpression of hypoxia\u2010inducible factor 1 alpha in common human cancers and their metastases","volume":"59","author":"Zhong H","year":"1999","journal-title":"Cancer Res"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2006.114033","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2006.114033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T13:18:16Z","timestamp":1697030296000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2006.114033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,24]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1113\/jphysiol.2006.114033"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2006.114033","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,24]]}}}