{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:17:49Z","timestamp":1761844669741},"reference-count":52,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Merck Incorporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p> Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region and the pre-B\u00f6tzinger complex (pre-B\u00f6tC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O<jats:sub>2<\/jats:sub>) during 10 days of exposure to CIH in chronically instrumented awake wild-type (WT) and HO-1 null mice (HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>). HO-1 was induced within the C1 and pre-B\u00f6tC regions after 1 day of CIH. There were no significant differences in the baseline respiratory parameters between WT and HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>. Prior to CIH, acute hypoxia increased respiratory frequency in both WT and HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>; however, minute diaphragm electromyogram activity increased in WT but not HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>. The hypoxic respiratory response after 1 and 10 days of CIH was restored in HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>. CIH resulted in an initial significant decline in 1) the hypoxic sigh frequency response, which was restored in WT but not HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>, and 2) the baseline sympathetic activity in WT and HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>, which remained stable subsequently in WT but not in HO-1<jats:sup>\u2212\/\u2212<\/jats:sup>. We conclude that 1) CIH induces expression of HO-1 in the C1 and pre-B\u00f6tC regions within 1 day and 2) HO-1 is necessary for hypoxia respiratory response and contributes to the maintenance of the hypoxic sigh responses and baseline sympathetic activity during CIH. <\/jats:p>","DOI":"10.1152\/japplphysiol.00036.2016","type":"journal-article","created":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T01:53:11Z","timestamp":1473385991000},"page":"944-952","source":"Crossref","is-referenced-by-count":8,"title":["Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice"],"prefix":"10.1152","volume":"121","author":[{"given":"Jag","family":"Sunderram","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New 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