Moderate and severe hypoxia elicit divergent effects on cardiovascular function and physiological rhythms

Melissa A. Allwood, Brittany A. Edgett, Ashley L. Eadie, Jason S. Huber, Nadya Romanova, Philip J. Millar, Keith R. Brunt, Jeremy A. Simpson

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Key points: In the present study, we provide evidence for divergent physiological responses to moderate compared to severe hypoxia, addressing an important knowledge gap related to severity, duration and after-effects of hypoxia encountered in cardiopulmonary situations. The physiological responses to moderate and severe hypoxia were not proportional, linear or concurrent with the time-of-day. Hypoxia elicited severity-dependent physiological responses that either persisted or fluctuated throughout normoxic recovery. The physiological basis for these distinct cardiovascular responses implicates a shift in the sympathovagal set point and probably not molecular changes at the artery resulting from hypoxic stress. Abstract: Hypoxia is both a consequence and cause of many acute and chronic diseases. Severe hypoxia causes hypertension with cardiovascular sequelae; however, the rare studies using moderate severities of hypoxia indicate that it can be beneficial, suggesting that hypoxia may not always be detrimental. Comparisons between studies are difficult because of the varied classifications of hypoxic severities, methods of delivery and use of anaesthetics. Thus, to investigate the long-term effects of moderate hypoxia on cardiovascular health, radiotelemetry was used to obtain in vivo physiological measurements in unanaesthetized mice during 24 h of either moderate (FIO2 = 0.15) or severe (FIO2 = 0.09) hypoxia, followed by 72 h of normoxic recovery. Systolic blood pressure was decreased during recovery following moderate hypoxia but increased following severe hypoxia. Moderate and severe hypoxia increased haeme oxygenase-1 expression during recovery, suggesting parity in hypoxic stress at the level of the artery. Severe but not moderate hypoxia increased the low/high frequency ratio of heart rate variability 72 h post-hypoxia, indicating a shift in sympathovagal balance. Moderate hypoxia dampened the amplitude of circadian rhythm, whereas severe disrupted rhythm during the entire insult, with perturbations persisting throughout normoxic recovery. Thus, hypoxic severity differentially regulates circadian blood pressure.

Original languageEnglish
Pages (from-to)3391-3410
Number of pages20
JournalJournal of Physiology
Volume596
Issue number15
DOIs
Publication statusPublished - Aug 1 2018

Bibliographical note

Funding Information:
This work was funded in part by the Canadian Institutes of Health Research (Grant # MOP111159) (JAS), the Natural Sciences and Engineering Research Council of Canada (to JAS and KRB and PJM) and the Heart and Stroke Foundation of Canada (to JAS and KRB). JSH is supported by Natural Sciences and Engineering Research Council of Canada graduate scholarship. ALE is supported by a Nova Scotia Health Research Foundation Scotia Scholars Award and New Brunswick Innovation Foundation Research Assistantships Initiative. MAA was supported by the Queen Elizabeth Graduate Scholarship in Science and Technology and an Ontario Graduate Scholarship. BAE was supported by funds from GlycoNet. We further acknowledge J. Southen and B. Southen of London, Ontario, for their philanthropic support. JAS is a new investigator with the Heart and Stroke Foundation of Ontario.

Publisher Copyright:
© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society

ASJC Scopus Subject Areas

  • Physiology

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