Connexin 40 is essential for hypoxic pulmonary vasoconstriction
Bibliographic record
Abstract
Hypoxic pulmonary vasoconstriction (HPV) has traditionally been attributed exclusively to O 2 sensing in pulmonary vascular smooth muscle cells (PASMC). Yet, the predominant site of gas exchange, and hence, the ideal site for O 2 sensing is in pulmonary capillaries, where PASMCs are absent. The spatial separation between a capillary O 2 sensor and PASMC in upstream arterioles would require a retrograde propagation of signals along the endothelial layer. Connexin 40 (Cx40) is expressed in lung endothelial cells and mediates conducted responses in the systemic circulation. Here, in isolated mouse lungs, we tested our hypothesis that Cx40 plays a critical role in HPV. HPV was quantified as increase in pulmonary artery pressure (PAP) in response to hypoxic ventilation (1% F i O 2 ). Intrinsic pulmonary vascular resistance (R 0 ) was determined by nonlinear regression analysis of pressure‐flow curves. Hypoxia‐induced increases in PAP and R 0 were attenuated by 75% in lungs perfused with the nonspecific gap junction blocker 18α‐glycyrrhetinic acid, by 55% with Cx40 specific mimetic peptide Gap27 40 , and by 64% in Cx40 −/− mice. The role of Cx40 is specific for HPV, since the vasoconstriction response to angiotensin II remained unaffected in all groups. Our data demonstrate a critical role of Cx40 in HPV, and suggest that microvascular endothelial cells may propagate the hypoxic signal to upstream arterioles via endothelial Cx40.
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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) | 0.001 | 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".