Cutaneous Blood Flow during Intradermal Exogenous Nitric Oxide Administration in Young and Older Adults: Roles for Cyclooxygenase and Calcium‐Activated Potassium Channels?
Bibliographic record
Abstract
Nitric oxide (NO) increases cutaneous blood flow. We hypothesized that cutaneous blood flow during intradermal administration of sodium nitroprusside (SNP, a NO donor) is in part regulated by cyclooxygenase (COX) and calcium‐activated potassium (KCa) channels in young adults. We also hypothesized that these contributions are diminished in older adults as ageing can reduce COX‐derived vasodilator prostanoids and downregulate KCa channels. In 10 young (3 males and 7 females, 23 ± 5 years) and 10 older (3 males and 7 females, 54 ± 4 years) adults, cutaneous vascular conductance (CVC) was measured at four intradermal forearm skin sites receiving 1) Ringers (Control), 2) 50 m M tetraethylammonium (TEA), a non‐specific KCa channel blocker, 3) 10 m M ketorolac, a non‐specific COX inhibitor, or 4) 50 m M TEA + 10 m M ketorolac. All skin sites were co‐infused with incremental doses of SNP (0.005, 0.05, 0.5, 5, 50 m M each for 25 min). Compared to the Control site, CVC during SNP administration was similar at the ketorolac site (0.005–50m M , all P > 0.05) but was lower at the TEA and TEA + ketorolac sites (0.005–5m M , all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to the Control site during SNP administration (0.005–0.5m M , all P < 0.05), but this increase disappeared when TEA was co‐administered (all P > 0.05). TEA alone did not modulate CVC during SNP administration in older adults (0.005–50m M , all P > 0.05). We show that during intradermal exogenous NO administration, KCa channels, but not COX, contribute to cutaneous blood flow regulation in young adults, while COX reduces cutaneous blood flow by attenuating KCa channel‐dependent cutaneous vasodilation in older adults. Support or Funding Information This study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014), and by Canada Foundation for Innovation (Leaders Opportunity Fund, 22529) (funds held by Dr. Glen P. Kenny).
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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 | 0.000 |
| 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".