Natriuretic Peptide Receptor‐C Agonist Attenuates the Enhanced Expression of Gqα, PLCβ1 Proteins and Vascular Smooth Muscle Cell Hypertrophy From Spontaneously Hypertensive Rats: Role of ROS and ROS‐Mediated Signalling
Bibliographic record
Abstract
Hypertension is associated with vascular remodelling due to hyper‐proliferation and hypertrophy of vascular smooth muscle cells (VSMCs). We earlier showed the implication of enhanced expression of Gqα and PLCβ1 proteins in VSMCs from 16‐week‐old spontaneously hypertensive rats (SHR). The present study was undertaken to investigate whether C‐ANP 4–23 , a natriuretic peptide receptor‐C (NPR‐C) agonist that has been shown to inhibit vasoactive peptide‐induced enhanced protein synthesis in VSMCs, could attenuate VSMC hypertrophy in rat models of cardiac hypertrophy and to explore the underlying mechanisms contributing to this inhibition. For these studies, aortic VSMCs from 16‐week‐old SHR were used. The protein synthesis, a marker of hypertrophy, was determined by ( 3 H) leucine incorporation and the expression of proteins was determined by Western blotting. The protein synthesis was significantly enhanced in VSMC from SHR as compared to WKY and C‐ANP 4–23 treatment attenuated the enhanced protein synthesis to WKY control levels. In addition, the enhanced expression of Gqα and PLCβ1 proteins in VSMC's from SHR was attenuated by C‐ANP 4–23 treatment. Furthermore, C‐ANP 4–23 also attenuated the enhanced levels of superoxide anion (O 2 − ), NADPH oxidase activity, the increased expression of NOX4, p47phox and p22phox, as well as the enhanced phosphorylation of ERK1/2, AKT1/2 and c‐Src. In conclusion, these results indicate that C‐ANP 4–23 , via the activation of NPR‐C, attenuates VSMC hypertrophy through its ability to decrease the over‐expression of Gqα, PLCβ1 proteins, enhanced oxidative stress and MAPK/AKT signalling pathway. Thus, it can be suggested that C‐ANP 4–23 , an activator of NPR‐C, may be used as a therapeutic agent for the treatment of vascular complications associated with hypertension and atherosclerosis Support or Funding Information Supported by grants from Canadian Institutes of Health Research and Heart and Stroke Foundation of Canada.
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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 | 0.000 | 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".