Propagation of Capillary‐initiated Conducted Vasodilation in Skeletal Muscle – A Novel Paracrine Signaling Pathway
Bibliographic record
Abstract
Coordination of arteriolar vasodilation is required for increases in blood flow to specific capillaries supplying active skeletal muscle fibers. Capillary stimulation results in a directional path of conducted upstream dilation to supplying arterioles resulting in increased capillary perfusion. This demonstrates the prominent role of capillaries directing blood flow recruitment in skeletal muscle tissue; however, mechanisms governing this response are not well defined. Cell membrane hemi‐channels known as pannexins have been implicated in arterial vascular control. Pannexins release adenosine triphosphate (ATP) into the extra‐cellular space and activate purinergic receptors on local and neighbouring cells. Activated purinergic receptors can thereafter promote pannexin‐mediated ATP release and subsequent purinergic receptor activation along capillaries, propagating paracrine cell‐to‐cell communication. We sought to determine the role of endothelial cell purinergic receptors in the propagation of capillary‐initiated conducted vasodilatory responses expressed at supplying terminal arterioles in skeletal muscle. Using intravital video microscopy of the hamster cremaster, we stimulated a local capillary site by (i) micropipette application of vasoactive drugs: potassium chloride (KCl; 10mM; n=5), adenosine (ADO, 10 −4 M; n=6), pinacidil (PIN, 10 −5 M; n=8), S‐nitroso‐N‐acetylpenicillamine (SNAP, nitric oxide donor; 10 −6 M; n=11), and acetylcholine (ACh; 10 −4 mM; n=4); and (2) microelectrode stimulation of skeletal muscle fibers underlying a small group of capillaries (15 contractions per minute, 20Hz contraction frequency, 250ms train duration; n=10). Subsequent diameter change was measured at the upstream supplying arteriole in the absence and presence of suramin (non‐specific P 2x and P 2y antagonist; 10 −5 M) applied via micropipette at a capillary site between the initiating capillary stimulation site and upstream arteriolar observation site. Arteriolar diameter increased significantly by 33% following muscle fiber stimulation, and by 35%, 35%, 32%, 24%, and 33% respectively, following micropipette application of vasoactive drugs (KCl, ADO, PIN, SNAP, and ACh) at the capillary. In the presence of suramin, conducted arteriolar dilatory responses were significantly attenuated by 29% following muscle fiber contraction under capillaries, and by 86%, 45%, 61% and 36% respectively, following micropipette application of KCl, ADO, PIN and SNAP to the capillary. In contrast, suramin had no effect on the conducted vasodilatory responses initiated by capillary exposure to ACh, highlighting the divide between ACh‐dependent mechanisms responsible for propagation of vasodilation at upstream arterioles, and those relevant to vasoactive products of muscle contraction. These novel data demonstrate a role for purinergic receptors in the propagation of a dilatory response along capillaries, expressed at the arteriolar level. Additionally, these findings implicate a novel paracrine signaling pathway in capillary‐initiated conducted vasodilation in skeletal muscle arterioles. Support or Funding Information Research funded by NSERC
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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".