Changes in aldehyde dehydrogenase 2 expression in rat blood vessels during glyceryl trinitrate tolerance development and reversal
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Recent studies have suggested an essential role for aldehyde dehydrogenase 2 (ALDH2) in the bioactivation of organic nitrates such as glyceryl trinitrate (GTN). In the present study, we utilized an in vivo GTN tolerance model to further investigate the role of ALDH2 in GTN bioactivation and tolerance. EXPERIMENTAL APPROACH: We assessed changes in aortic ALDH activity, and in ALDH2 protein expression in various rat blood vessels (aorta, vena cava, femoral artery and femoral vein) during continuous GTN exposure (0.4 mg·h⁻¹ for 6, 12, 24 or 48 h) or after a 1-, 3- or 5-day drug-free period following a 48 h exposure to GTN, in relation to changes in vasodilator responses to GTN and in vascular GTN biotransformation. KEY RESULTS: A decrease was observed in both ALDH2 protein expression (80% in tolerant veins and 30% in tolerant arteries after 48 h exposure to GTN) and aortic ALDH activity, concomitant with decreased vasodilator responses to GTN and decreased aortic GTN biotransformation. However, after a 24 h drug-free period following 48 h of GTN exposure, vasodilator responses to GTN and aortic GTN biotransformation activity had returned to control values, whereas vascular ALDH2 expression and aortic ALDH activity were still significantly depressed, and remained so for 3-5 days following cessation of GTN exposure. CONCLUSIONS AND IMPLICATIONS: The dissociation of reduced ALDH activity and ALDH2 expression from the duration of the impaired vasodilator and biotransformation responses to GTN in nitrate-tolerant blood vessels, suggests that factors other than changes in ALDH2-mediated GTN bioactivation contribute to nitrate tolerance.
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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 | 0.001 | 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".