Nitric oxide attenuates the enhanced expression of Giα proteins in vascular smooth muscle cells from spontaneously hypertensive rats: molecular mechanisms (1065.15)
Bibliographic record
Abstract
We have previously shown that the nitric oxide donor, SNAP, decreased the expression of Giα proteins and associated functions in A10 vascular smooth muscle cells. The present study was undertaken to investigate if SNAP can also decrease the expression of Giα proteins and associated signaling in aortic vascular smooth muscle cells (VSMC) from 12‐week‐old Wistar‐Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) and to further explore the underlying mechanism(s). Treatment of VSMC with SNAP (100 µM) for 24h decreased the expression of Giα‐2, ‐3 proteins. This decrease was subverted by inhibiting peroxynitrite with wither Mn (III) tetrakis (4‐benzoic acid) porphyrin (MnTBAP) or uric acid, and by inhibiting MEK with PD98059. However, inhibition of guanylate cyclase by 1H‐(1, 2, 4) oxadiazolo (4, 3‐a) quinoxalin‐1‐one (ODQ) was unable to restore the SNAP‐induced decrease in Giα‐2, ‐3. In addition, the enhanced activity of NADPH oxidase and protein levels of its subunits (Nox‐4, p47phox and p22phox) were decreased by SNAP. The decreased expression of NADPH oxidase subunits was restored towards control levels by MnTBAP. Furthermore, SNAP treatment decreased the enhanced levels of O2‐, TBARS and protein carbonyl in SHR to control levels. SNAP also attenuated the increased phospholyration of PDGFR, EGFR and IGF‐1R and c‐Src. These results suggest that SNAP decreased the enhanced expression of Giα proteins in VSMC from SHR by attenuating the increased oxidative stress, growth factor receptor activation and ensuing ERK1/2 signaling and not by a cGMP‐dependent mechanism. Grant Funding Source : CIHR
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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) | 0.000 | 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) | 0.002 | 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".