Selective cyclo‐oxygenase‐2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence
Why this work is in the frame
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Bibliographic record
Abstract
1. Selective inhibitors of cyclo-oxygenase-2 have been shown to be effective anti-inflammatory drugs with reduced gastrointestinal toxicity relative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, we examined the possibility that selective COX-2 inhibition, by blocking prostacyclin synthesis, would increase blood pressure and cause leukocyte adherence and platelet aggregation. 2. Normal rats and rats with hypertension induced by chronic administration of Nomega-nitro-L-arginine methylester were given celecoxib (10 mg kg(-1)) daily for 3 weeks. Celecoxib significantly elevated of blood pressure in both the normal and hypertensive rats (mean increase of >33 mm Hg after 3 weeks). 3. In normal rats, celecoxib had no effect on serum 6-keto prostaglandin (PG)F(1alpha) levels. Hypertensive rats exhibited a significant increase (82%) in serum 6-keto PGF(1alpha) levels, and this was reduced to the levels of normal rats by treatment with celecoxib. 4. Rats treated with celecoxib exhibited significant increases in weight gain (20%), plasma arginine-vasopressin levels (148%) and plasma urea (69%) relative to vehicle-treated controls. Plasma creatinine levels were unaffected by treatment with celecoxib, while plasma renin levels were significantly decreased (30%) relative to controls. 5. Superfusion of mesenteric venules with celecoxib (3 microM) in vivo resulted in significant increases in leukocyte adherence to the endothelium in both normal and hypertensive rats. 6. These studies suggest that suppression of COX-2 significantly influences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.
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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 | 0.001 |
| 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 it