Relaxant effect of atorvastatin on isolated rat gastric fundus strips: implications for Ca<sup>2+</sup>-signalling mechanisms
Bibliographic record
Abstract
Statins are determined to have various pleiotropic effects apart from their lipid-lowering properties. Herein, we investigated the direct effects of atorvastatin on gastric smooth muscle tone. Atorvastatin effectively relaxed isolated rat gastric fundus strips precontracted with acetylcholine, potassium chloride, and serotonin. Incubation of the strips with nitric oxide synthase inhibitor, l-NOARG (10 −4 M, 20 min), l-type voltage-operated Ca 2+ channel (VOCC) blocker, nifedipine (10 −6 M, 30 min), K ATP channel blocker, glibenclamide (10 −5 M, 30 min), or precursor of cholesterol, mevalonate (10 −2 M, 45 min) did not change the relaxations to atorvastatin. However, pretreatment of fundus strips with atorvastatin (3×10 −5 –3×10 −4 M, 30 min) inhibited the contractions to calcium chloride (10 −4 –10 −1 M), acetylcholine (10 –4 M), and caffeine (20 mM) in the calcium-free medium. Moreover, atorvastatin reduced the contractions induced by sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA) inhibitor, cyclopiazonic acid (10 −7 –3×10 −5 M). The current study demonstrated that atorvastatin produces an acute relaxant effect on gastric fundus strips, which appears to be mediated by several Ca 2+ -signalling mechanisms such as the blockade of l-type VOCC-independent Ca 2+ entry, decrease in smooth muscle Ca 2+ sensitivity, inhibition of IP 3 - and ryanodine-sensitive intracellular stores to mediate Ca 2+ release, as well as the activation of SERCA. This acute relaxing effect seems unlikely to be related with nitric oxide, K ATP channels, and the mevalonate pathway.
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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) | 0.001 | 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 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".