Angiotensin II Disrupts Neurovascular Coupling by Potentiating Calcium Increases in Astrocytic Endfeet
Bibliographic record
Abstract
Background Angiotensin II (Ang II), a critical mediator of hypertension, impairs neurovascular coupling. Since astrocytes are key regulators of neurovascular coupling, we sought to investigate whether Ang II impairs neurovascular coupling through modulation of astrocytic Ca 2+ signaling. Methods and Results Using laser Doppler flowmetry, we found that Ang II attenuates cerebral blood flow elevations induced by whisker stimulation or the metabotropic glutamate receptors agonist, 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid ( P <0.01). In acute brain slices, Ang II shifted the vascular response induced by 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid towards vasoconstriction ( P <0.05). The resting and 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid–induced Ca 2+ levels in the astrocytic endfeet were more elevated in the presence of Ang II ( P <0.01). Both effects were reversed by the AT1 receptor antagonist, candesartan ( P <0.01 for diameter and P <0.05 for calcium levels). Using photolysis of caged Ca 2+ in astrocytic endfeet or pre‐incubation of 1,2‐Bis(2‐aminophenoxy)ethane‐ N,N,N',N' ‐tetra‐acetic acid tetrakis (acetoxymethyl ester), we demonstrated the link between potentiated Ca 2+ elevation and impaired vascular response in the presence of Ang II ( P <0.001 and P <0.05, respectively). Both intracellular Ca 2+ mobilization and Ca 2+ influx through transient receptor potential vanilloid 4 mediated Ang II‐induced astrocytic Ca 2+ elevation, since blockade of these pathways significantly prevented the intracellular Ca 2+ in response to 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid ( P <0.05). Conclusions These results suggest that Ang II through its AT1 receptor potentiates the astrocytic Ca 2+ responses to a level that promotes vasoconstriction over vasodilation, thus altering cerebral blood flow increases in response to neuronal activity.
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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".