A critical role for connexin 40 in hypoxia induced pulmonary vasoconstriction
Bibliographic record
Abstract
The ideal location for O 2 sensor is at the site of gas exchange, i.e. in lung capillaries where pulmonary vascular smooth muscle cells (PASMCs) are absent. We speculated that hypoxic signals may be propagated retrogradely along the endothelial layer from lung capillaries to PASMC‐bearing upstream arterioles via connexin 40 (Cx40), causing hypoxic pulmonary vasoconstriction (HPV). In isolated mouse lungs, we detected an ~60% attenuation of HPV in wild type (WT) mice with nonspecific gap junction blocker 18α–glycyrrhetinic acid or Cx40 specific mimetic peptide Gap27 40 . HPV was similarly reduced in Cx40 −/− mice while the response to Angiotensin II was unmitigated. The physiologic relevance of Cx40 in HPV‐dependent ventilation‐perfusion (V/Q) matching was evaluated in ventilated mice after tracheal instillation of saline. The resulting hypoxemia was prominent in Cx40 −/− mice as compared to WT (paO 2 : 99±8 vs. 76±12 mmHg). By fluorescence imaging of di‐8‐ANEPPS loaded isolated mouse lungs, we detected a hypoxia‐induced membrane depolarization in extra‐alveolar capillary and arteriolar endothelial cells of WT lungs that was attenuated in Cx40 −/− mice. Our data identify a critical role for Cx40 in HPV and V/Q matching, suggesting that hypoxia is sensed in lung capillary endothelial cells and propagated as membrane depolarization via Cx40 from capillaries to upstream arterioles.
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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) | 0.002 | 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".