Resistance arteries of Ang II-infused osteopetrotic mice show reduced impairment of endothelial function, oxidative stress, and vascular remodeling: Role of inflammation and mCSF in hypertension
Bibliographic record
Abstract
Vascular damage induced by angiotensin (Ang) II may be partially mediated by vascular inflammation and reactive oxygen species. Atherogenesis is inhibited in homozygous osteopetrotic (op/op) mice lacking macrophage colony-stimulating factor (mCSF). No data are currently available on the interaction between mCSF deficiency and hypertension. We investigated the effects of Ang II on function and structure, NAD(P)H oxidase activity and vascular inflammation in resistance mesenteric arteries from op/op mice. Adult op/op, heterozygous (op/+), and wild type (+/+) mice were infused with Ang II (1000 ng/kg/min, sc) or vehicle for 14 days. Blood pressure (BP) was measured by radio-telemetry. Vascular structure and fnction were assessed in mesenteric resistance arteries mounted on a pressurized myograph. NADPH oxidase activity was evaluated by lucigenin chemiluminescence and macrophage infiltration was assessed with confocal microscopy.Ang II elevated SBP (mmHg) only in +/+ and op/+ (168±9 and 177±2, P<0.01 vs. controls), but not in op/op mice (151±7 vs. control, 143±4). Mesenteric arteries from Ang II-treated op+/+ and op/+ mice exhibited reduced Ach-mediated-relaxation (maximal relaxation respectively 64% and 67% vs. 84% and 93% in controls, P<0.05), which was unaffected by L-NAME. Op/op mice infused with Ang II showed significantly less endothelial dysfunction as measured by Ach-induced relaxation (87% vs. 96% in controls), which were further impaired by pre-incubation with L-NAME. Arteries from Ang II-infused +/+ and op/+ mice showed increased media:lumen ratio (P<0.01) and media thickness (P<0.01), neither of which were different in op/op mice compared with untreated counterparts. Media cross sectional area was increased (P<0.05) by Ang II only in +/+ mice. NADPH oxidase activity and macrophage infiltration were increased by Ang II infusion in op+/+ (P<0.05) but unchanged in op/+ and op/op mice compared to controls. These findings indicate that mCSF-deficient mice were more resistant to endothelial dysfunction, vascular remodeling and oxidative stress induced by Ang II, suggesting a critical role of proinflammatory mediators in vascular injury associated with Ang II-induced hypertension.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".