Does ovariectomy exacerbate the cardiorespiratory and metabolic consequences of moderate intermittent hypoxia in female rats?
Bibliographic record
Abstract
Intermittent hypoxia (IH) is a major consequence of sleep apnea (SA). IH causes respiratory dysfunction and contributes to numerous co-morbidities of SA including hypertension and obesity. The fact that menopause increases the prevalence of SA and related diseases in women indicates the importance of loss of ovarian function in the pathophysiology. Here, we determined whether experimental loss of ovarian function (ovariectomy; OVX) exacerbates the cardiorespiratory and metabolic consequences of IH. We explored neuroendocrine changes by assessing hormones known to be involved in energy balance, respiratory control, and stress responses (leptin, ACTH and corticosterone). We subjected adult (8 weeks) Sprague Dawley female rats to bilateral OVX (n = 13) or sham operation (n = 14). Rats were housed in pairs, and after two weeks of recovery, animals were exposed to room air (control; n = 16) or to a 7-day moderate IH protocol (n = 11). Within their cage, rats intermittently received a nitrogen-enriched hypoxic mixture, followed by room air for reoxygenation. Each bout of hypoxia lasted 30 seconds (nadir FIO 2 = 0.10) and was followed by 5-minutes of reoxygenation (10 cycles/h, for 8hrs between 10h-18h). Apnea frequency, acute responses to hypoxia (FIO 2 = 0.12; 120 sec) and hypercapnia (FICO 2 = 0.05; 10 min) were measured by whole-body plethysmography. Blood pressure was assessed by the tail cuff method, and body weight was followed throughout the protocol. Plasma corticosterone and leptin were measured by multiplex assays. OVX increased apneic events, whereas IH reduced them; with the highest frequency observed in OVX females maintained in normoxia. Ventilatory responses (hypoxia and CO 2 ) and blood pressure were not affected by IH or OVX. Over the course of the protocol, OVX increased weight gain whereas IH induced weight loss. OVX (but not IH) increased ACTH and corticosterone. IH (but not OVX) reduced leptin. Correlation matrix analysis showed that weight gain was the best predictor of apnea frequency (r = 0.759; p = 0.03). We conclude that loss of ovarian function and related weight gain have the greatest impact on respiratory function during sleep. Additionally, OVX-related activation of the stress pathways may contribute to this process. These results fail to demonstrate a role for OVX in exacerbating the cardiorespiratory and metabolic consequences of IH. Lack of weight gain following IH likely contributes to this finding. This study is supported by operating grants from the Canadian Institutes of Health Research (RK and VJ). NJM is supported by a Sentinel North Partnered Research Chair in Sleep Pharmacometabolism and a Canada Research Chair in Metabolism and Sleep Neurobiology. MG received a doctoral scholarship from the Fonds de Recherche du Québec — Santé (FRQS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".