Vasoconstrictor responses, and underlying mechanisms, to isoprostanes in human and porcine bronchial arterial smooth muscle
Bibliographic record
Abstract
We investigated the effects of five different isoprostanes (8-iso PGE1, 8-iso PGE2, 8-iso PGF1alpha, 8-iso PGF2alpha and 8-iso PGF2beta) on vasomotor tone in human and porcine bronchial arterial tissues. In the human bronchial arteries, 8-iso PGE2 and 8-iso PGF2alpha evoked powerful constrictions (magnitudes several fold greater than the responses to high millimolar KCl) with negative log concentration causing 50% excitation (EC50) values of 6.8 and 6.5, respectively; 8-iso PGE1 was less potent (EC50 not calculated, since a clear peak contraction was not obtained), while the other isoprostanes were largely ineffective. In the porcine arteries, on the other hand, all three F-ring isoprostanes as well as 8-iso PGE2 evoked constrictor responses, although the peak magnitudes were approximately 50% of the KCl-evoked response; 8-iso PGE2 and 8-iso PGF2alpha were the most potent, with negative log EC50 values of 6.5. We next sought to characterize the signaling pathways underlying the vasoconstrictor responses to 8-iso PGE2, since this was the most potent of the isoprostanes we tested. These responses were largely reversed by the thromboxane A2-selective (TP) prostanoid receptor antagonist ICI 192605 (10-8 m; 4(Z)-6-[(2,4,5 cis)2-(2-chlorophenyl)-4-(2-hydroxy phenyl)1,3-dioxan-5-yl]hexenoic acid) as well as by the nonspecific tyrosine kinase inhibitor genistein (10-5 and 10-4 m), and were reversed approximately 50% by the Rho-kinase inhibitor Y27632 (10-5 m; (+)-(R)-trans-4-(1-aminoethyl)-N-(pyridyl) cyclohexanecarboxamide dihydrochloride). We conclude, therefore, that 8-iso PGE2 constricts bronchial vasculature through the activation of TP receptors, which in turn trigger tyrosine kinase and Rho-kinase activities, resulting in powerful vasoconstriction. These findings are highly relevant to lung transplantation and to exercise-induced asthma.
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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".