Neuronal HIF-1α in the nucleus tractus solitarius contributes to ventilatory acclimatization to hypoxia.

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The Journal of physiology


KEY POINTS: We hypothesized that hypoxia inducible factor 1α (HIF-1α) in central nervous system (CNS) respiratory centers is necessary for ventilatory acclimatization to hypoxia (VAH); VAH is a time-dependent increase in baseline ventilation and the hypoxic ventilatory response (HVR) occurring over days to weeks of chronic sustained hypoxia (CH). Constitutive deletion of HIF-1α in CNS neurons in transgenic mice tended to blunt the increase in HVR that occurs in wild-type mice with CH. Conditional deletion of HIF-1α in glutamatergic neurons of the NTS during CH significantly decreased ventilation in acute hypoxia but not normoxia in CH mice. These effects are not explained by changes in metabolic rate nor CO2 and there were no changes in the HVR in normoxic mice. HIF-1α mediated changes in gene expression in CNS respiratory centers are necessary in addition to plasticity of arterial chemoreceptors for normal VAH.

ABSTRACT: Chronic hypoxia (CH) produces a time-dependent increase of resting ventilation and the hypoxic ventilatory response (HVR) that is called ventilatory acclimatization to hypoxia (VAH). VAH involves plasticity in arterial chemoreceptors and the central nervous system (e.g. nucleus tractus solitarius, NTS) but signals for this plasticity are not known. We hypothesized hypoxia inducible factor 1-α (HIF-1α), an O


Pulmonary Medicine