Differential activation of extracellular signal-regulated protein kinase 1/2 and p38 mitogen activated-protein kinase by AT1 receptors in vascular smooth muscle cells from Wistar–Kyoto rats and spontaneously hypertensive rats
Bibliographic record
Abstract
OBJECTIVES: The present study investigates effects of angiotensin II on activation of extracellular signal-regulated protein kinase (ERK) 1/2, p38 mitogen activated-protein kinase (p38MAPK) and c-Jun amino terminal kinase (JNK) in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). METHODS: Vascular smooth muscle cells (VSMC) from mesenteric arteries of Wistar-Kyoto (WKY) rats and SHR were studied. Angiotensin II-induced phosphorylation of ERK1/2, JNK and p38MAPK were assessed by Western blot analysis. c-fos mRNA expression by angiotensin II was determined by reverse transcriptase-polymerase chain reaction in the absence and presence of PD98059, selective inhibitor of ERK1/2-dependent pathways and SB202190, selective p38MAPK inhibitor. RESULTS: Angiotensin II increased phosphorylation of ERK1/2 and p38MAPK, but not JNK. Responses were significantly increased in SHR compared with WKY. Irbesartan, AT1 receptor antagonist, but not PD123319, AT2 receptor blocker, abolished angiotensin II-induced effects. PP2, selective Src inhibitor, decreased angiotensin II-mediated activation of MAP kinases. Angiotensin II increased c-fos mRNA expression in SHR and had a small stimulatory effect in WKY. These actions were inhibited by PD98059, whereas SB202190 had no effect. CONCLUSIONS: Angiotensin II-induced activation of vascular ERK1/2 and p38MAPK is increased in SHR. These effects are mediated via AT1 receptors, which activate Src-dependent pathways. Overexpression of c-fos mRNA in SHR is due to ERK1/2-dependent, p38MAPK-independent pathways. Our results suggest that angiotensin II activates numerous MAP kinases in VSMCs and that differential activation of these kinases may be important in altered growth signaling in VSMCs from SHR.
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How this classification was reachedexpand
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) | 0.002 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".