Differential Calcium Regulation by Hydrogen Peroxide and Superoxide in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats
Bibliographic record
Abstract
We investigated the role of reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2) and superoxide anion (*O2-) in the regulation of vascular smooth muscle cell (VSMC) Ca2+ concentration ([Ca2+]i) and vascular contraction and assessed whether redox-dependent Ca2+ signaling and contraction are altered in hypertension. VSMCs and mesenteric arteries from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were studied. Cells were stimulated with H2O2 (10(-4) mol/l) or LY83583 (*O2- generator, 10(-5) mol/l). [Ca2+]i and cytosolic *O2- were measured by fura-2AM and tempo-9-AC fluorescence respectively. L-type and T-type Ca2+ channels were assessed using verapamil/diltiazem and mibefradil respectively and mRNA and protein expression of these channels was assessed by real-time PCR and immunoblotting respectively. H2O2 time-dependently increased [Ca2+]i and contraction with significantly greater effects in SHR versus WKY (P < 0.001). LY83583 increased [Ca2+]i in both strains, but responses were blunted in SHR. Removal of extracellular Ca2+ abrogated [Ca2+]i responses to H2O2 and *O2-. Verapamil and diltiazem, but not mibefradil, significantly decreased H2O2 -induced [Ca2+]i responses with greater effects in SHR (P < 0.01). L-type and T-type Ca2+ channel inhibition reduced LY83583-mediated [Ca2+]i increase only in WKY cells. Both types of Ca2+ channels were expressed (mRNA and protein) in VSMCs from WKY and SHR, with greater abundance in SHR than WKY (2- to 3-fold). These results demonstrate that ROS increase vascular [Ca2+]i and contraction, primarily via extracellular Ca2+ influx. Whereas responses to H2O2 are enhanced, *O2- -mediated actions are blunted in SHR. These effects may relate to differential activation of Ca2+ channels by H2O2 and *O2-. Enhanced activation of L-type Ca2+ channels and increased Ca2+ influx by H2O2 may contribute to increased Ca2+ signaling in VSMCs from SHR.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".