L‐Tryptophan methyl ester Evokes Endothelium‐, Serotonin‐Independent Biphasic Vasoconstrictor and Vasodilator Responses in Rat Mesenteric Arterioles
Bibliographic record
Abstract
The vascular effects of L‐tryptophan (L‐W) are unknown. The in vitro responses to L‐W and its cell permeant analog, L‐W methyl ester (L‐Wme), were compared in third order branches of mesenteric arterioles of 12 week old male Sprague Dawley rats. While L‐W had no effect, L‐Wme evoked concentration‐dependent vasoconstriction (10 – 160 μM) followed by vasodilatation (300 μM – 2.5 mM) in both endothelium‐intact and endothelium‐denuded vessels. While 5‐HT antagonist, ketanserin (50 nM), shifted the responses to 5‐HT (EC 50 Control 107 ± 10 nM vs. Treatment 32 ± 6 μM; p<0.001), it failed to affect the responses to L‐Wme. The inclusion of transient receptor potential channel (TRPC) blocker, 2‐aminoethoxy phenyl borate (10 μM) or the voltage‐gated Ca 2+ channel blocker, verapamil (10 μM), abolished the bipahsic responses to L‐Wme. L‐Wme evoked (1 μM ‐ 2.5 mM) vasodilatation was more sensitive in potassium chloride depolarized (IC 50 330 ± 19 μM; I max 95%) than in phenylephrine constricted vessels (IC 50 767 ± 23 μM; I max 96%). These data suggest that the cell permeant amino acid, L‐Wme, exerts endothelium‐/serotonin‐independent responses that could be due to activation and blockade of Ca 2+ influx occurring through either the TRPC and/or the voltage‐gated Ca 2+ channels present on vascular smooth muscle cells of resistance type vessel. This confirms a direct role for L‐W analogs in the regulation of vascular smooth muscle tone.
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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".