Role of Mitochondrial Aldehyde Dehydrogenase in Nitroglycerin-Mediated Vasodilation: Observations Concerning the Dose–Response Relationship
Bibliographic record
Abstract
The mechanism of the bioactivation of nitroglycerin has long been controversial, with a number of suggested enzymatic pathways. More recently, aldehyde dehydrogenase-2 (ALDH-2) has been reported as the important enzyme involved in the bioactivation of nitroglycerin at therapeutically relevant concentrations. Other previously described enzyme systems can also bioactivate nitroglycerin, but only at concentrations, which are significantly higher than achieved in clinical practice. This study investigated the vascular response to nitroglycerin given over a wide range of concentrations in subjects with and without the ALDH-2 Glu504Lys polymorphism, a common genetic variant that greatly reduces the activity of ALDH-2 (n = 10 in both groups). Forearm blood flow (FBF) responses to a brachial artery infusion of nitroglycerin were assessed using venous occlusion plethysmography. Intra-arterial infusion of nitroglycerin caused a significant increase in FBF beginning at 0.464 µg/min with increasing responses seen in both groups at all infusion rates. However, there were no differences in the FBF responses to nitroglycerin in those with and without the ALDH-2 polymorphism, suggesting that ALDH-2 is not solely responsible for the bioactivation of nitroglycerin at either low (therapeutically relevant) or high concentrations of nitroglycerin.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".