Intravascular Pressure Augments Cerebral Arterial Constriction by Inducing Voltage‐Insensitive Ca2+ Waves
Bibliographic record
Abstract
This study examined whether elevated intravascular pressure stimulates asynchronous Ca 2+ waves and if their generation contributes to myogenic tone development. Rat cerebral arteries were mounted in an arteriograph, pressurized (20–100 mmHg) and examined under a variety of experimental conditions. Diameter and membrane potential (V M ) were monitored using conventional techniques; Ca 2+ wave generation and myosin light chain (MLC 20 )/MYPT1 phosphorylation were assessed by confocal microscopy and western blot analysis, respectively. Elevating intravascular pressure increased the proportion of smooth muscle cells firing Ca 2+ waves as well as event frequency. Ca 2+ wave augmentation occurred primarily at lower intravascular pressures and ryanodine, an agent that depletes the sarcoplasmic reticulum (SR), eliminated these events. Ca 2+ wave generation was voltage‐insensitive as Ca 2+ channel blockade and perturbations in extracellular [K + ] had little effect on measured parameters. Ryanodine‐induced inhibition of Ca 2+ waves attenuated myogenic tone and MLC 20 phosphorylation without altering arterial V M . Thapsigargin also attenuated Ca 2+ waves, pressure‐induced constriction and MLC 20 phosphorylation. The SR‐driven component of the myogenic response was proportionally greater at lower intravascular pressures and subsequent MYPT1 phosphorylation measures revealed that SR Ca 2+ waves facilitate pressure‐induced MLC 20 phosphorylation through mechanisms that include myosin light chain phosphatase inhibition. Our findings show that mechanical stimuli augment Ca 2+ wave generation and that these transient events facilitate tone development particularly at lower intravascular pressures by providing a proportion of the Ca 2+ required to directly control MLC 20 phosphorylation.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.001 | 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".