Reduction of blood pressure by store‐operated calcium channel blockers
Bibliographic record
Abstract
The voltage-operated Ca(2+) channels (VOCC), which allow Ca(2+) influx from the extracellular space, are inhibited by anti-hypertensive agents such as verapamil and nifedipine. The Ca(2+) entering from outside into the cell triggers Ca(2+) release from the sarcoplasmic reticulum (SR) stores. To refill the depleted Ca(2+) stores in the SR, another type of Ca(2+) channels in the cell membrane, known as store-operated Ca(2+) channels (SOCC), are activated. These SOCCs are verapamil and nifedipine resistant, but are SKF 96465 (SK) and gadolinium (Gd(3+) ) sensitive. Both SK and Gd(3+) have been shown to reduce [Ca(2+) ]i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd(3+) produced a dose-dependent reduction in blood pressure in rat. The combination of SK and verapamil produced an additive action in lowering the blood pressure. Furthermore, SK, but not Gd(3+) suppressed proliferation of vascular smooth muscle cells in the absence or presence of lysophosphatidic acid (LPA). SK decreased the elevation of [Ca(2+) ]i induced by LPA, endothelin-1 (ET-1) and angiotensin II (Ang II), but did not affect the norepinephrine (NE)-evoked increase in [Ca(2+) ]i . On the other hand, Gd(3+) inhibited the LPA and Ang II induced change in [Ca(2+) ]i , but had no effect on the ET-1 and NE induced increase in [Ca(2+) ]i . The combination of verapamil and SK abolished the LPA- or adenosine-5'-triphosphate (ATP)-induced [Ca(2+) ]i augmentation. These results suggest that SOCC inhibitors, like VOCC blocker, may serve as promising drugs for the treatment of hypertension.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".