Activators of SK <sub>Ca</sub> and IK <sub>Ca</sub> channels enhance agonist‐evoked vasodilation and endothelial NO synthesis
Bibliographic record
Abstract
Pharmacologic blockade of small‐ and intermediate conductance, Ca 2+ ‐activated K + channels (SK Ca and IK Ca channels, respectively) is known to interfere with agonist‐evoked vasorelaxation via nitric oxide (NO) synthesis and the pathway involving an ‘endothelium‐derived hyperpolarizing factor’ (EDHF). Given these important functional effects of vascular SK Ca and IK Ca channels, we examined the hypothesis that activation of these channels may augment the normal cellular pathway(s) underlying agonist‐mediated vasorelaxation. In single human umbilical vein endothelial cells (HUVECs), the SK Ca /IK Ca channel openers NS309 and DCEBIO in combination (1 μM each) enhanced ATP‐evoked cytosolic Ca 2+ elevation and NO synthesis, as monitored by Fluo−3 and DAF‐FM, respectively. NS309 and DCEBIO also enhanced ATP‐induced membrane hyperpolarization. On their own, these channel openers produced significant membrane hyperpolarization and modest Ca 2+ elevations, but did not induce NO production. In rat cremaster arterioles pressurized to ∼50 mm Hg, NS309 and DCEBIO alone evoked a significant reduction of myogenic tone and further augmented ACh‐induced vasodilation. Removing the endothelium by passage of an air bubble through the vessel lumen significantly diminished the vasodilatory responses to either ACh or NS309 and DCEBIO, indicating a predominant endothelial site of action for these 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) | 0.000 | 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) | 0.002 | 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".