Inhibition of inducible nitric oxide synthase and superoxide production reduces matrix metalloproteinase-9 activity and restores coronary vasomotor function in rat cardiac allografts
Bibliographic record
Abstract
OBJECTIVE: Oxidants such as nitric oxide (NO) and superoxide are involved in coronary endothelial dysfunction, an early event in the process of allograft coronary atherogenesis, possibly by activation of matrix metalloproteinases (MMPs) and extracellular matrix proteins. We investigated the contribution of inducible nitric oxide synthase (iNOS) derived NO and superoxide on (MMP)-9 activity and to changes in coronary vasomotor function in rat cardiac allografts. METHODS AND RESULTS: An allogenic (Brown Norway to Lewis rats) heterotopic cardiac transplantation model was used to study the effect of continuous treatment with a selective iNOS inhibitor; N-(3-(aminomethyl) benzyl) acetamidine (1400W), and polyethylene glycol conjugated superoxide dismutase (SOD) either alone or in combination on coronary vasomotor dysfunction. 1400W or SOD 24 h alone or their combination improved endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) coronary flow reserve and inhibited enhanced MMP-9 protein and activity. In addition, histopathological study revealed that either 1400W or SOD or their combination reduced superoxide production and nitrotyrosine protein. CONCLUSION: The present study demonstrates for the first time that selective iNOS inhibition or SOD treatment reduces enhanced MMP-9 protein and activity associated with improvement of both, endothelium-dependent and -independent coronary vasomotor function in rat cardiac allografts. This is accompanied by reduction of nitrotyrosine and superoxide production. This suggests that the proteolytic enzyme MMP-9 is an effector molecule of oxidant-mediated coronary vasomotor dysfunction.
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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 | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".