Sex Differences in Vascular Reactivity During Acute and Chronic Hypoxia

• Author / Creator

  Vanden Berg, Emily R

• BACKGROUND: Current evidence suggests that males and females regulate resting blood pressure differently. This may be a function of altered sympathetic activity, neurovascular coupling, or vascular smooth muscle receptor sensitivity. In this study, we wished to determine the role of α1-adrenoreceptors in vascular reactivity in both males and females with acute hypoxia exposure, and with early (day 2-3) and late (day 7-9) acclimatization to high-altitude hypoxia (White Mountain, CA; 3,800m). We hypothesized that 1) α1-adrenergic sensitivity would be attenuated with exposure to hypoxia, reducing vascular reactivity to sympathetic excitation and 2) females would exhibit lesser reactivity in comparison to males.

  METHODS: We studied a convenience sample of 7 males and 6 females at three time points: 1) low altitude (Calgary AB, 1,045m) breathing room air (normoxia; LOW) and acute isocapnic hypoxia (PETO2 ~48mmHg; PETCO2 ~37mmHg; ACUTE); 2) during early (day 2-3; EARLY) and 3) late (day 7-9; LATE) acclimatization at high altitude (White Mountain, CA; 3,800m) breathing room air (PETO2 ~50mmHg) and hyperoxia (100% O2). Heart rate (HR; bpm), mean arterial pressure (MAP; mmHg), and blood oxygen saturation (SpO2; %) were collected beat-by-beat. Participants performed a cold pressor test (CPT) to assess integrated cardiovascular reactivity to a sympathetic stressor. To isolate α1-adrenergic receptor sensitivity, we delivered a graded series of phenylephrine hydrochloride (PE) injections. Statistical analysis included a mixed model ANOVA, and Holm-Sidak post hoc tests when we identified main effects (α<0.05).

  RESULTS: α1-Adrenergic specific MAP sensitivity decreased with hypoxia (main effect P=0.0027). Similarly, hypoxic conditions were associated with attenuated maximal responses to CPT (main effect, P=0.0013). Males and females experienced similar blunting of α1-adrenergic mechanisms with hypoxia (P=0.6675). Though resting MAP and maximal responses to CPT were not statistically different between males and females (both P0.05), indicating adrenergic desensitization is the result of adaptive processes and not due to the acute effects of hypoxia.

  CONCLUSIONS: Here, we have demonstrated that α1-adrenergic receptor mediated vascular reactivity is attenuated with high-altitude hypoxia similarly in males and females. This may be due to receptor desensitization caused by increased basal sympathetic nervous activity and resulting plasma neurotransmitter concentrations. However, there is evidence that males and females may adapt to tonically elevated sympathetic activity differently, which warrants further investigation. This study offers insight into resting and reflexive vascular regulation with acclimatization to hypoxia and has implications for males and females ascending to high altitude.

• Subjects / Keywords

  • hypoxia
  • sex differences
  • vascular
  • sympathetic
  • altitude

• Graduation date

  Fall 2022

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-k4qw-az61

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.