The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse <scp>L</scp>-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38
Bibliographic record
Abstract
Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1± 0.18 mm from 4.6 ± 0.13 mm (p < 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1 ± 0.1 mm and 4.8 ± 0.2 mm, respectively (p < 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131% ± 3% of the control value, which was associated with significant increment in ERK1/2 to 143% ± 5% of the control value (p < 0.05). Ordonafil and sildenafil decreased cell surface area to 95% ± 3% and 90% ± 1% of the control value, respectively. Both drugs decreased ERK1/2 to 88% ± 4% of the control value. Calcineurin activity was significantly decreased after 1 h of treatment with 0.1 mg·L(-1) ordonafil (1.15 ± 0.05, p < 0.05). For sildenafil (0.1 mg·L(-1)), calcineurin activity significantly decreased only after 24 h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1 mg·L(-1)). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes.
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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) | 0.000 | 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".