Roles of HIF‐1 on ventilatory, metabolic and mitochondrial cox responses to hypoxia in rats
Bibliographic record
Abstract
The lack of oxygen at high altitudes presents constraints for mammals. One of the mechanisms involved in the response to hypoxia is the stabilization of HIF‐1 (Hypoxia Inducible Factor 1) which contributes to ventilatory and metabolic responses, reduces mitochondrial respiration and stimulates anaerobic glycolysis. Upon acute hypoxia exposure, the expression of HIF‐1 reaches peak levels after a few hours of hypoxic exposure. In rats, however, the expression of HIF‐1 in hypoxia appears to be limited, as are the ventilatory and metabolic responses in comparison to other species better adapted to altitude. The purpose of this study is to better understand the interactions between hypoxia and HIF‐1 and to determine if there are other mechanisms possibly related to hypoxic responses. To this end, we measured ventilation and metabolic rate under resting conditions (whole body plethysmography) and mitochondrial respiration of the cerebral cortex and liver (oxygraphy) in adult male SD rats exposed in normoxia (21% O2 ‐ 6h), in hypoxia (10% O2 ‐ 6h), in normoxia after injection of a HIF‐1 stabilizer (deferoxamine; 100mg/kg), and in hypoxia after injection of a HIF‐1 inhibitor (2‐methoxyestradiol; 5mg/kg). Hypoxia reduces metabolism, increases minute ventilation and respiratory rate by 171 and 59% respectively and increases cytochrome c oxidase (COX) activity by an average of 72% in the cortex. Stabilization of HIF‐1 in normoxia doesn't result in any of these responses. However, inhibition of HIF‐1 in hypoxia decreases ventilatory responses by 30% for minute ventilation and 23% for respiratory rate and completely blocks the increase in COX activity. HIF‐1 would therefore be totally responsible for the IV complex responses observed in hypoxia, but would only be partially involved in the ventilatory response. There thus appears to be an interaction between HIF‐1 and other factors induced in hypoxia to establish ventilatory responses.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".