Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats
Bibliographic record
Abstract
Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension. In this study, we tested the hypothesis that a nitric oxide-releasing derivative of naproxen would ameliorate hypertension in the rat. Hypertension was induced by partially occluding one renal artery (the "2K,1C" model), and 2 wk later the rats started receiving naproxen, the nitric oxide-releasing derivative HCT-3012, or vehicle each day for 2 wk. Naproxen significantly exacerbated the hypertension. HCT-3012 significantly reduced blood pressure relative to both the naproxen- and vehicle-treated groups. Both naproxen and HCT-3012 markedly suppressed whole blood thromboxane B(2) synthesis. In studies of anesthetized rats, naproxen significantly enhanced the late hypertensive response to endothelin-1 and significantly blunted the early hypotensive response. In contrast, HCT-3102 did not affect either response to endothelin-1. In vitro, HCT-3012 significantly reduced the responsiveness of aortic rings to the contractile effects of phenylephrine. These studies suggest that HCT-3012 reduces blood pressure in hypertensive rats, not simply through the vasodilatory actions of the nitric oxide it releases, but through alterations in the responsiveness of the vasculature to endogenous pressor agents.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".