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

Josh T. Arnold, Stephen J. Bailey, Simon G. Hodder, Naoto Fujii, Alex B. Lloyd

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
8 Downloads (Pure)


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, 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.

Original languageEnglish
Pages (from-to)1207-1218
Number of pages12
JournalEuropean Journal of Applied Physiology
Issue number4
Early online date9 Feb 2021
Publication statusPublished - Apr 2021
Externally publishedYes


  • Anapyrexia
  • Cold
  • Hypoxia
  • Nitric oxide
  • Shivering
  • Vasoconstriction

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