Endothelin-1-Mediated Wave-Like [Ca<sup>2+</sup>]<sub>i</sub> Oscillations in Intact Rabbit Inferior Vena Cava
Why this work is in the frame
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Bibliographic record
Abstract
Endothelin-1 (ET1) is an endogenous vasoconstrictor released by the vascular system to regulate the contractility of vascular smooth muscle cells (VSMC). It is implicated in the pathogenesis of hypertension and diabetic vasculopathy. In rabbit inferior vena cava (IVC), 10 n<i>M</i> ET1 induces tonic contraction mainly via type A endothelin receptor activation. Using confocal imaging of Fluo-3 loaded in thein situ VSMC within the intact IVC, we found that ET1 elicited [Ca<sup>2+</sup>]<sub>i</sub> oscillations with an average frequency of 0.31 ± 0.01 Hz. These [Ca<sup>2+</sup>]<sub>i</sub> oscillations occurred as repetitive Ca<sup>2+</sup> waves traveling along the longitudinal axis of the cells with an average velocity of 29 ± 3 µm/s. The Ca<sup>2+</sup> waves were not synchronized between neighboring VSMC nor were they propagated between them. Nifedipine (10 µ<i>M</i>) inhibited the tonic contraction by 27.0 ± 5.0% while SKF96365 (50 µ<i>M</i>) abolished the remaining contraction. In a parallel Ca<sup>2+</sup> study, nifedipine reduced the frequency of the oscillations to 0.22 ± 0.01 Hz while SKF96365 abolished the remaining [Ca<sup>2+</sup>]<sub>i</sub> oscillations. Subsequent application of 25 m<i>M</i> caffeine elicited no further Ca<sup>2+</sup> signal. Thus, we conclude that ET1 stimulates tonic contraction in the rabbit IVC by inducing [Ca<sup>2+</sup>]<sub>i</sub> oscillations and that stimulated Ca<sup>2+</sup> entry through both the L-type voltage-gated Ca<sup>2+</sup> channels and a nifedipine-resistant and SKF96365-sensitive pathway is crucial for the maintenance of [Ca<sup>2+</sup>]<sub>i</sub> oscillations and tonic contraction.
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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 | 0.016 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it