Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice

作者：Sunderram Jag^*; Semmlow John; Patel Pranav; Rao Harshit; Chun Glen; Agarwala Priya; Bhaumik Mantu; Oanh Le Hoang; Lu Shou En; Neubauer Judith A

来源：Journal of Applied Physiology, 2016, 121(4): 944-952.

DOI：10.1152/japplphysiol.00036.2016

• heme oxygenase
• pre-Botzinger complex
• C1 sympathoexcitatory region
• sighs
• spectral analysis of heart rate variability
• chronic intermittent hypoxia

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-Botzinger complex (pre-BotC). 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-2) 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-BotC 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, minute diaphragm electromyogram activity 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 an initial significant decline in 1) the hypoxic sigh frequency response, which was restored in WT but not HO-1(-/-), and 2) the baseline sympathetic activity in WT and HO-1(-/-), which remained stable subsequently in WT but not in HO-1(-/-). We conclude that 1) CIH induces expression of HO-1 in the C1 and pre-BotC 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.

• 出版日期2016-10-1
• 单位rutgers