Thromboxane A2 Receptors Mediate Pulmonary Hypertension in 60% Oxygen–exposed Newborn Rats by a Cyclooxygenase-independent Mechanism
Bibliographic record
Abstract
Endothelin-1 (ET-1) mediates the development of pulmonary hypertension (PHT) in newborn rats exposed to 60% O(2) for 14 days, a model for human chronic neonatal lung injury. ET-1 production by d-14 rat pulmonary artery smooth muscle cells in vitro was markedly increased by thromboxane (TX) A(2) receptor agonists and inhibited by a competitive antagonist. We hypothesized that stimulation of the TX A(2) receptor contributed to O(2)-mediated PHT in vivo. Newborn rat pups received daily intraperitoneal injections of L670596, a competitive TX A(2) receptor antagonist, or 5,5-dimethyl-3-(3-fluorophenyl)4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU), a cyclooxygenase-2 inhibitor, during 14 days of 60% O(2) or air exposure. L670596, but not DFU, prevented 60% O(2)-mediated right ventricular and small pulmonary vessel smooth muscle hypertrophy. Lung ET-1 content was significantly reduced by L670596 in 60% O(2)-exposed animals. We conclude that TX A(2) receptor activation, though not by TX A(2), caused upregulation of ET-1 and PHT in this model. A likely mediator is the stable lipid peroxidation product, 8-iso-prostane, which acts as an incidental ligand of the TX A(2) receptor and is a potent inducer of ET-1 production by cultured d-14 rat pulmonary artery smooth muscle cells in vitro.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".