Ovariectomy, but Not Estrogen Deficiency, Increases CYP4A Modulation of 1-Adrenergic Vasoconstriction in Aging Female Rats
Bibliographic record
Abstract
BACKGROUND: Postmenopausal women are more likely to develop cardiovascular disease (CVD) than premenopausal women. Increased vasoconstriction in the peripheral vasculature may underlie this risk. In vascular smooth muscle, cytochrome P450 4A (CYP4A) enzymes form the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). CYP4A modulation of alpha(1)-adrenergic vasoconstriction is increased in aging male rats; however, this pathway has not been investigated in aging females. To generate an appropriate model of menopause, we ovariectomized aged Sprague-Dawley rats to create an aged, ovarian-depleted phenotype. Because estrogen has profound effects on the peripheral vasculature, we also determined the effect of estrogen replacement on CYP4A modulation of vasoconstriction. METHODS: Aged (15-16 months) rats were assigned to be intact or ovariectomized. Ovariectomized rats received either placebo (OVX) or 17beta-estradiol (OVX-E) subcutaneously for 4 weeks. Mesenteric arteries were isolated and constricted with the alpha(1)-adrenergic agonist phenylephrine or intraluminal pressure in the absence or presence of the CYP4A inhibitor, DDMS. RESULTS: Ovariectomy increased CYP4A modulation of alpha(1)-adrenergic vasoconstriction. This was unaffected by estrogen replacement. Arteries from OVX-E animals exhibited increased phenylephrine sensitivity and forced dilation relative to arteries from intact and OVX animals. Myogenic tone was increased in both OVX and OVX-E animals relative to intact rats; however, CYP4A inhibition had no effect on myogenic tone in any group. CONCLUSIONS: In aged female rats, ovariectomy caused an increase in CYP4A modulation of alpha(1)-adrenergic vasoconstriction that was not prevented by estrogen replacement. Future study of these pathways may provide important targets for the prevention of CVD in aging women.
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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".