Interplay between NO, prostaglandins and K <sub>ATP</sub> channels in the lymphatic pumping dysfunction observed during experimental intestinal inflammation
Bibliographic record
Abstract
Lymphatic vessels rhythmically contract to actively propel lymph. This function, critical to tissue fluid homeostasis and immune cell trafficking is impaired in Crohn's disease and in the guinea‐pig model of TNBS ileitis, suggesting compromised lymph flow and lymphatic vessels potential players in the disease. Nitric oxide (NO) and prostaglandins (PGs), abundantly produced during intestinal inflammation, are known to activate ATP‐sensitive potassium (K ATP ) channels expressed in lymphatic muscle. Our aim was to assess the role of K ATP channels, NO and PGs in inflammation‐induced lymphatic pumping dysfunction. After induction of intestinal inflammation, mesenteric lymphatics were collected for qPCR analysis, or isolated to assess their contractile and electrophysiological properties. Expression of mRNA for K ATP channel subunits Kir6.1 and SUR2B, nitric oxide synthase iNOS and cyclooxygenase COX2 was significantly upregulated in lymphatics from TNBS‐compared to sham‐treated animals. Vessels from TNBS‐treated animals were dilated, quiescent, with strongly hyperpolarized muscle. Administration of the K ATP blocker glibenclamide, iNOS inhibitor 1400W and COX inhibitor indomethacin restored pumping and depolarized lymphatic muscle. Our findings suggest that NO and PGs mediate lymphatic contractile dysfunction seen in TNBS‐treated animals via K ATP channel opening. Supported by CIHR
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".