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 FiO2) with placebo ingestion, 3) normoxia with 13 mmol nitrate ingestion, 4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45-mins to determine heat loss, and at the point of shivering onset to determine 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-mins, 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-mins, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. Conclusion: This data improves our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.