Effect of Phenylephrine on Cerebrovascular Regulation: A Translational Perspective
Bibliographic record
Abstract
Background Phenylephrine is an alpha 1‐adrenergic receptor (α1R) agonist. Evidence indicates activation of α1Rs can initiate both vasoconstrictor and dilator signaling. How phenylephrine affects cerebrovascular regulation remains unclear. Methods A retrospective analysis of data examining cerebral perfusion and blood pressure during systemic phenylephrine infusion in humans and swine was completed. Follow‐up experiments examining cerebral hemodynamics during intracarotid arterial infusion of phenylephrine in anesthetized swine were performed. Ex vivo experiments were conducted on isolated porcine cerebral arteries. Results Systemic phenylephrine infusion increased indices of cerebrovascular resistance in both humans ( P =0.0423) and swine ( P <0.0001) but did not decrease perfusion. Intracarotid phenylephrine infusion did not alter cerebrovascular resistance, but increased perfusion in control conditions ( P =0.0045), whereas resistance increased ( P ≤0.0155) without altered perfusion during NOS (nitric oxide synthase) inhibition conditions. α1Rs were detected on both extraluminal and intraluminal aspects of cerebral arteries, reflecting a population of vascular smooth muscle and endothelial α1Rs, respectively. Extraluminal phenylephrine caused vasoconstriction whereas intraluminal phenylephrine elicited an endothelium‐dependent NO‐mediated dilation. NOS inhibition enhanced phenylephrine‐induced vasoconstriction in third‐order branch of the middle cerebral artery, but not the first‐order or second‐order pial arteries ( P =0.0267), and this corresponded with an increased ratio of phosphorylated to total endothelial NOS protein content in third‐order versus first‐order and second‐order arteries ( P ≤0.0022). Phenylephrine‐induced constriction was greatest in first‐order arteries ( P =0.0419), and this corresponded with increased perivascular adrenergic innervation and α1R protein content in first‐order versus second‐order and third‐order arteries ( P ≤0.0054). Conclusions Neither systemic nor intracarotid phenylephrine infusion compromised cerebral perfusion, possibly related to increased endothelial NO signaling and reduced α1R density in downstream pial arteries.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".