Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice
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Bibliographic record
Abstract
Deoxycorticosterone acetate (DOCA)-salt hypertension has an important endothelin-1 (ET-1)-dependent component. ET-1-induced vascular damage may be mediated in part by oxidative stress and vascular inflammation. Homozygous osteopetrotic (Op/Op) mice, deficient in macrophage colony-stimulating factor (m-CSF), exhibit reduced inflammation. We investigated in osteopetrotic (Op/Op) mice the effects of DOCA-salt hypertension on vascular structure, function, and oxidative stress, the latter as manifested by reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity. Mice were implanted with DOCA (200 mg/mouse, under 5% isofluorane anesthesia) and given saline for 14 days. Systolic blood pressure (mmHg) was significantly increased (146 +/- 2 and 138 +/- 1; P < 0.001 vs. basal 115 +/- 3 and 115 +/- 3, respectively) by DOCA-salt in wild-type (+/+) and heterozygous (Op/+) mice, but not in Op/Op mice (130 +/- 1 vs. basal 125 +/- 3). Norepinephrine contractile response was significantly enhanced, while acetylcholine endothelium-dependent vasodilation was significantly impaired in DOCA-salt-treated +/+ and Op/+ mice compared with control mice. No changes in norepinephrine-induced contraction and acetylcholine-induced relaxation were observed in DOCA-salt Op/Op mice. DOCA-salt +/+ and Op/+ mice had significantly increased mesenteric resistance artery media-to-lumen ratio and media cross-sectional area, neither of which were altered in Op/Op mice. Basal vascular superoxide production and NAD(P)H oxidase activity, vascular cell adhesion molecule-1 expression, and macrophage infiltration were significantly increased only in DOCA-salt +/+ mice. Thus m-CSF-deficient mice developed less endothelial dysfunction, vascular remodeling, and oxidative stress induced by DOCA-salt than +/+ and Op/+ mice, suggesting that inflammation may play a role in DOCA-salt hypertension, a model that results in part from effects of ET-1, which has proinflammatory actions.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 it