Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold

Purpose: This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control, and thermometrics in response to cold stress. Method: Eleven male volunteers underwent passive cooling at 10 °C air temperature across four conditions: (1) normoxia with placebo ingestion, (2) hypoxia (0.130 F_iO₂) with placebo ingestion, (3) normoxia with 13 mmol nitrate ingestion, and (4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45 min to determine heat loss, and at the point of shivering onset to determine the thermogenic thermoeffector threshold. Result: Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45 min, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5), or delta change in rectal temperature (p = 0.7) over 45 min, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. Conclusion: These data improve our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.