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 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) | 0.001 | 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 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".