Chronic inhibition of nitric oxide synthase modulates calcium handling in rat heart
Bibliographic record
Abstract
Systemic infusion of nitric oxide synthase (NOS) inhibitors increases peripheral vascular resistance due to inhibition of endothelial NOS leading to the activation of the arterial baroreceptor mechanisms and inhibition of central sympathetic outflow. In the current study, we explored that systemic NOS blockage activates protein kinase A (PKA)-mediated signaling pathway through maintained cGMP-dependent protein kinase (PKG) activation. Rats were treated with 3 different concentrations of N(ω)-nitro-l-arginine methyl ester (L-NAME) for 14 days. Systemic L-NAME treatment induced a dose-dependent increase in blood pressure and increased mRNA levels of atrial natriuretic peptide (ANP) and phosphorylation levels of p44/42 MAPK without any change in cardiac mass. The cardiac cGMP levels and PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) (Ser239) did not alter in any group. At the highest dose of treatment (100 mg/kg per day), PKA-mediated phosphorylations of VASP (Ser157) and troponin I (TnI) (Ser23/24) were enhanced significantly indicating the increase in PKA activation in response to chronic NOS blockage. Alterations in both phosphorylated phospholamban (Ser16/Thr17) and sarcoplasmic/endoplasmic Ca2+-ATPase (SERCA2) levels can increase cytosolic Ca2+ load and impair Ca2+ handling. Our data suggest that the increased PKA activation in response to chronic NOS blockage appears to be responsible for cardiac abnormalities that occur due to prolonged L-NAME treatment.
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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".