Aging Increases Cytochrome P450 4A Modulation of α1-Adrenergic Vasoconstriction in Mesenteric Arteries
Bibliographic record
Abstract
Aging is associated with peripheral vascular dysfunction. In vascular smooth muscle, cytochrome P450 4A (CYP4A) enzymes form the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE acts as an intracellular messenger to modulate vasoconstriction induced by various agonists, including the alpha1-adrenergic agonist phenylephrine (PE) and endothelin-1 (ET-1). Eicosanoids produced by CYP4A contribute to the elevated vascular tone in hypertension, but the effects of advanced age on CYP4A modulation of vasoconstriction are unknown. Mesenteric arteries were isolated from young (3 to 4 months) and aged (17 to 18 months) Sprague-Dawley rats. Vasoconstriction was induced with PE or ET-1 in the absence or presence of the CYP4A inhibitor DDMS and/or the ETA inhibitor BQ123. CYP4A inhibition with DDMS significantly reduced PE sensitivity in aged rats, but it had no effect in young. Furthermore, in aged rats only, ETA inhibition reduced PE sensitivity while combined inhibition of CYP4A and ETA had no additional effect, suggesting that the pathways work in concert in aging. Exogenous ET-1 constriction was not altered by DDMS in young or aged rats. Overall, our data indicate that aging increases the contribution of CYP4A to alpha1-adrenergic vasoconstriction in systemic arteries. Understanding aging-related changes in vascular function is important for development of novel targets for the prevention of cardiovascular disease.
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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) | 0.000 | 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) | 0.001 | 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".