Essential role of src in angiotensin ii-mediated vascular smooth muscle ca2+ and contractile responses
Bibliographic record
Abstract
Tyrosine kinases may regulate Ang II-induced vascular contraction. However the specific kinases involved are unknown. This study investigated the regulatory role of c-Src in Ca2+ and contractile responses mediated by Ang II in human vascular smooth muscle cells (VSMC). Cultured VSMC derived from resistance arteries from healthy humans were studied. Intracellular free Ca2+ concentration ([Ca2+]i) was measured by fura 2, c-Src phosphorylation was determined by Western blot, and inositol 1,4,5-trisphosphate (IP3) production was determined by radioimmunoassay. Contractile responses were examined in intact arteries mounted as pressurized systems. Ang II rapidly increased c-Src activity (4-5 fold increase). PP2, the selective Src inhibitor, but not PP3, the inactive analogue, blocked this effect. Ang II induced a biphasic [Ca2+]i response (Emax=636±123 nmol/L, pD2=8.2±0.61). PP2 but not PP3 attenuated (p<0.01) [Ca2+]i transients. Cells were electroporated with anti-c-Src antibodies, which significantly reduced the Ang II-stimulated [Ca2+]i signal. PP2 attenuated (p<0.01) Ang II-induced production of IP3 and the Ang II-stimulated IP3-sensitive [Ca2+]i transient. Ang II increased vascular contraction (Emax=40±6.5%). PP2 inhibited (p<0.05) contractile responses (Emax=7.8±0.08%), whereas contraction was unaltered by PP3 (Emax =35±4.5%). Our results indicate that 1) in human VSMCs, c-Src is an important upstream regulator of [Ca2+]i-dependent pathways, 2) c-Src modulates intracellular Ca2+ homeostasis by influencing IP3-induced Ca2+i mobilization and 3) c-Src influences Ang II-stimulated vascular contraction. These findings suggest an essential role for c-Src [Ca2+]i regulation and contraction in Ang II-stimulated vascular smooth muscle.
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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 | 0.001 | 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 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".