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-Bötzinger complex (pre-BötC). 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%O2) during 10 days of exposure to CIH in chronically instrumented awake wild type (WT) and HO-1 null mice (HO-1-/-). HO-1 was induced within the C1 and pre-BötC regions after 1 day of CIH. There were no significant differences in the baseline respiratory parameters between WT and HO-1-/-. Prior to CIH, acute hypoxia increased respiratory frequency in both WT and HO-1-/-, however, min EMGDi increased in WT but not HO-1-/-. The hypoxic respiratory response after 1 and 10 days of CIH was restored in HO-1-/- . CIH resulted in a initial significant decline in i) the hypoxic sigh frequency response that were restored in WT but not HO-1-/-. ii) Baseline sympathetic activity in WT and HO-1-/-, that remained stable subsequently in WT mice but not in HO-1 null mice. We conclude that: 1) CIH induces expression of HO-1 in the C1 and pre-BötC regions within 1 day; 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.
- Heme Oxygenase
- pre-Bötzinger Complex
- C1 sympathoexcitatory region
- Copyright © 2016, Journal of Applied Physiology