Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
OBJECTIVE: We tested the hypothesis that increased responsiveness of phospholipase D (PLD) to angiotensin II (Ang II) is associated with increased oxidative stress and exaggerated growth responses in vascular smooth muscle cells (VSMC) from untreated essential hypertensive patients. DESIGN: VSMCs from peripheral resistance arteries of normotensive and hypertensive subjects were studied. Production of reactive oxygen species (ROS) was measured with the fluoroprobe 5-(and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). PLD and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase were assessed with the inhibitors, dihydro-D-erythro-sphingosine (sphinganine) and diphenylene iodinium (DPI), respectively, and protein kinase C (PKC) effects were determined using chelerythrine chloride and calphostin C. PLD activity was measured by the transphosphatidylation assay. RESULTS: Ang II increased the CM-H2DCFDA fluorescence signal, derived predominantly from H2O2. Ang II-induced generation of DPI-inhibitable ROS was significantly enhanced in cells from hypertensives compared with normotensives (Emax = 72 +/- 2 versus 56.9 +/- 1.8 fluorescence units, P< 0.01). PLD inhibition attenuated Ang II-induced ROS generation, with greater effects in the hypertensive group than the normotensive group (delta = 42 +/- 3.3 versus 21 +/- 2 units). PKC inhibition partially decreased Ang II-elicited signals. Ang II-stimulated PLD activity and DNA and protein synthesis were significantly greater in cells from hypertensives than normotensives. These effects were normalized by DPI and sphinganine. CONCLUSIONS: Our results suggest that in essential hypertension enhanced oxidative stress and augmented growth-promoting actions of Ang II are associated with increased activation of PLD-dependent pathways. These processes may contribute to vascular remodeling in hypertension.
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.
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 | 0.000 |
| 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