Neuronal nitric oxide synthase (NOS) regulates leukocyte‐endothelial cell interactions in endothelial NOS deficient mice
Bibliographic record
Abstract
1. The present study was designed to examine the possible role of neuronal nitric oxide synthase (nNOS) in regulation of leukocyte - endothelial cell interactions in the absence of endothelial nitric oxide synthase (eNOS), using intravital microscopy of the cremasteric microcirculation of eNOS(-/-) mice. 2. Baseline leukocyte rolling and adhesion revealed no differences between wild-type and eNOS(-/-) mice in either the cremasteric or intestinal microcirculations. 3. Superfusion with L-NAME (100 microM) caused a progressive and significant increase in leukocyte adhesion in both wild-type and eNOS(-/-) mice, without detecting differences between the two strains of mice. 4. Superfusion with 7-nitroindazole (100 microM), a selective inhibitor of nNOS, had no effect on leukocyte adhesion in wild-type animals. However, it increased leukocyte adhesion significantly in eNOS(-/-) mice, which was reversed by systemic L-arginine pre-administration. 5. Stimulation of the microvasculature with H(2)O(2) (100 microM) induced a transient elevation in leukocyte rolling in wild-type mice. Conversely, the effect persisted during the entire 60 min of experimental protocol in eNOS(-/-) mice either with or without 7-nitroindazole. 6. Semi-quantitative analysis by RT - PCR of the mRNA for nNOS levels in eNOS(-/-) and wild-type animals, showed increased expression of nNOS in both brain and skeletal muscle of eNOS(-/-) mice. 7. In conclusion, we have demonstrated that leukocyte-endothelial cell interactions are predominantly modulated by eNOS isoform in postcapillary venules of normal mice, whereas nNOS appears to assume the same role in eNOS(-/-) mice. Interestingly, unlike eNOS there was insufficient NO produced by nNOS to overcome leukocyte recruitment elicited by oxidative stress, suggesting that nNOS cannot completely compensate for eNOS.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 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".