Tumor Necrosis Factor-α and Vascular Angiotensin II in Estrogen-Deficient Rats
Bibliographic record
Abstract
Alterations in the vascular angiotensin II system may play a role in the pathophysiology of vascular disease after menopause. In previous studies we have shown that an increase in tumor necrosis factor (TNF)-alpha levels in aging rats because of estrogen deficiency may result in vascular dysfunction. In this study we investigated the effect of TNF-alpha inhibition in angiotensin II modulation of vascular function in aging female animals. Female rats approaching reproductive senescence (12 to 15 months old) were ovariectomized and treated with placebo, estrogen, or a selective TNF-alpha inhibitor (etanercept) for 4 weeks. Expression of angiotensin II in mesenteric arteries was evaluated by immunofluorescence, and the expression of angiotensin-converting enzyme and angiotensin type I receptor (AT(1)R) was investigated by Western immunoblot. Vascular function was assessed in mesenteric arteries using the myograph system, and the role of endogenous angiotensin II on adrenergic vasoconstriction was evaluated in vitro by selective AT(1)R blockade (Candesartan; 10 micromol/L). Our data demonstrate that estrogen-depleted rats have higher serum levels of TNF-alpha and greater sensitivity to phenylephrine vasoconstriction compared with estrogen-replaced animals, which was attenuated by AT(1)R blockade. In vivo TNF-alpha inhibition or estrogen replacement reduced phenylephrine constriction of mesenteric arteries and decreased the modulation of this vasoconstriction by candesartan. These functional changes were accompanied by a reduction in the vascular expression of angiotensin II, angiotensin-converting enzyme, and AT(1)R. These observations indicate that upregulation of TNF-alpha during estrogen deficiency may contribute to enhance vascular constriction by altering the vascular angiotensin II system.
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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".