Effects of Glutathione-depleting Drug Buthionine Sulfoximine and Aging on Activity of Endothelium-derived Relaxing and Contracting Factors in Carotid Artery of Sprague–Dawley Rats
Bibliographic record
Abstract
The role of the antioxidant glutathione (GSH) in mediating endothelial (dys)function, and how that role may depend on age, is unclear. The main purpose of the current study was to investigate the effect of 10-day treatment with the GSH-depleting drug l-buthionine sulfoximine (BSO) on endothelium-derived relaxing factor and endothelium-derived contracting factor activities in the isolated common carotid artery (CCA) of Adult and Aging animals. CCA blood pressure and flow were unaffected by age or BSO. Endothelium-derived relaxing factor activity, examined in precontracted CCA as relaxation to cumulative acetylcholine (ACh), was largely nitric oxide synthase (NOS) mediated and was not different between Adult and Aging animals at lower ACh; however, at higher ACh, relaxation was blunted in Aging CCA, an effect abolished by cyclooxygenase (COX) inhibition but not by NOS inhibition nor by the reactive oxygen species (ROS) inhibitors 4-hydroxy-TEMPO or Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin,tetratosylate,hydroxide. Specific examination of endothelium-derived contracting factor activity in quiescent NOS-inhibited CCA established that higher ACh elicited a contractile response, ∼3.5-fold greater in Aging versus Adult CCA, which was abolished by COX-1-specific inhibition but unaffected by ROS inhibitors. Aging was unrelated to changes in liver or vascular tissue GSH or ROS content. BSO was effective in significantly decreasing GSH and increasing ROS content in both animal cohorts. However, NOS-mediated endothelium-derived relaxing factor activity was well preserved and age-related COX-mediated endothelium-derived contracting factor activity was unaffected in response to these BSO-induced perturbations, as were exogenous H2O2-stimulated NOS/non-NOS-mediated relaxation and COX-mediated contractile activities. These data suggest that, regardless of age, chronic partial depletion of GSH in vivo does not necessarily cause endothelium-dependent vasomotor dysfunction.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".