Sex Differences in Vascular Reactivity with Acute and Chronic Hypoxia
Bibliographic record
Abstract
Objective Males and females may respond differently to hypoxic exposure at high altitude. Females have reduced vascular resistance in response to hypoxia, possibly due to differences in adrenergic control. We investigated the role of sex in vascular control during hypoxia. We hypothesized females have reduced vasoreactivity to sympathetic stressors compared to males during acute and prolonged hypoxia exposure. Methods We studied a convenient sample of 7 males and 6 females at three time points: 1) low altitude (Calgary AB, 1100m) breathing room air (normoxia; LOW) and acute isocapnic hypoxia (P ET O 2 ~50mmHg; P ET CO 2 ~32mmHg; ACUTE); 2) during early (day 2‐3; EARLY) and 3) late (day 8‐10; LATE) acclimatization at high altitude (White Mountain, CA; 3800m) breathing room air (P ET O 2 ~50mmHg) and hyperoxia (100% O 2 ). Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (S p O 2 ) were collected beat‐by‐beat. Participants performed a cold pressor test (CPT) to assess integrated cardiovascular reactivity to a sympathetic stressor. To isolate α 1 ‐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 In response to CPT, peak change in MAP decreased with hypoxia duration (p<0.001). There was also a significant interaction between condition and sex (p=0.038). While LOW (+17.0±5.9mmHg) and ACUTE (+15.3±4.7mmHg) responses were not different (p=0.565), males showed a marked decrease in peak MAP response to CPT at EARLY (+10.2±4.9mmHg) and LATE (+9.8±5.4mmHg) compared to LOW (both p<0.001). Similarly, LOW (+11.8±8.4mmHg) and ACUTE (+8.2±3.8mmHg) peak MAP responses to CPT were not different in females (p=0.137). Though female responses decreased between LOW and EARLY (+6.3±3.3mmHg; p=0.042), they returned to similar values by LATE (+9.7±7.5mmHg; p=0.479). Adrenergic sensitivity slope was decreased at altitude (p=0.025) independent of sex (p=0.977). LOW (0.33±0.21) and ACUTE (0.22±0.10) sensitivity were not different (p=0.309). Notably, sensitivity was reduced at altitude at LATE (0.14±0.16; p=0.043), but not significantly at EARLY (0.16±0.18; p=0.051) compared to LOW. Hyperoxia did not correct CPT responses or PE adrenergic sensitivity to low altitude values at EARLY (p<0.001; p=0.01, respectively) nor LATE (p=0.013; p=0.042, respectively). Conclusions Our data indicate decreased α 1 ‐adrenergic responsiveness with acclimatization underlies blunted vascular reactivity in both sexes. However, female responses to CPT returned to low altitude values following 8 days at altitude, indicating differential adaptation. Additional mechanisms influencing the vascular response to stress (e.g. less neuropeptide mediated constriction, higher β‐adrenergic dilation) may account for lower responsiveness in females compared to males. Our results have implications for understanding vascular function at high altitude and in clinical conditions characterized by hypoxemia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".