Neuropeptide Y and Pial Artery Vasomotor Control: An Ordered Affair
Bibliographic record
Abstract
Evidence indicates sympathetic neurotransmitters influence cerebral vasomotor tone in a branch order‐dependent manner. Further, in addition to eliciting vasoconstriction, sympathetic co‐transmitter neuropeptide Y (NPY) may also elicit dilation in the cererbrovasculature depending on whether it acts on vascular smooth muscle or the endothelium. Herein, we investigated vasomotor responses to NPY in pial arteries (intracranial arteries on the surface of the brain) along the cerebrovascular tree. Female pigs (n=15, total arteries=88; age=2±0 months) were euthanized and their brains were harvested. First order (1A; n=7–8 per experiment), second order (2A; n=7–8 per experiment), and third order (3A; n=7–8 per experiment) pial arterial branches from the middle cerebral artery were dissected for pressure myography experiments. Following stabilization, NPY was administered either extra‐luminally (1e‐10 ‐‐to 1e‐6 M; half log doses, n=8 pigs) or intra‐luminally (1e‐9 M, n=7 pigs). To evaluate the contribution of nitric oxide (NO) on vasomotor responses to NPY, a subset of arteries were pre‐treated with a NO synthase (NOS) inhibitor (L‐NAME 3e‐4 M) 30 minutes prior to NPY administration. Whereas extra‐luminal NPY elicited vasoconstriction (24/24 arteries), intra‐luminal NPY tended to elicit vasodilation (16/21 arteries). Maximal vasoconstriction (% of baseline diameter) in response to extra‐luminal NPY was greater in 3a vs. 2a and 1a pial arteries (1a=13±1%; 2a=15±2%; *3a=23±4%; p≤0.01). Differences between 1a and 2a pial arteries were not significant (p=0.17). Pre‐treatment with a NOS inhibitor enhanced the maximal vasoconstriction in 1a, 2a and 3a pial arteries (grouped data; untreated=17±1%; *following NOS inhibition=29±1%; p<0.01). Dilation (% of baseline diameter) in response to intra‐luminal NPY was greater in 1a and 3a vs. 2a pial arteries (*1a=4±4%; 2a=−3±6%; *3a=9±4%; p≤0.01). Of note, whereas 86% of 1a and 3a pial arteries dilated, only 57% of 2a pial arteries dilated following transient exposure to intra‐luminal NPY. NOS inhibition abolished NPY‐induced dilation and promoted an NPY‐mediated vasoconstriction (grouped data; untreated=4±3%; *following NOS inhibition=−15±3%; p<0.01). In summary, NPY regulates cerebral vasomotor control through both vasoconstriction and dilation. These results indicate vasomotor responses to NPY are branch order‐dependent and most apparent in 3a pial arteries. NOS inhibition exacerbated NPY‐induced constriction and ablated NPY‐induced dilation, implicating NO signaling as a regulator of NPY‐dependent effects on cerebrovascular tone. Support or Funding Information This work was supported by a MU CVM COR grant and a SHRF Establishment grant (#4522).
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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".