Chronically Elevated Endothelin Levels Reduce Pulmonary Vascular Reactivity to Nitric Oxide
Bibliographic record
Abstract
UNLABELLED: Although local tissue activation of the endothelin (ET) system contributes to the development of pulmonary hypertension, the impact of isolated chronic plasma hyperendothelinemia on the pulmonary circulation is unknown. METHODS: Mini-osmotic pumps were implanted in rats to deliver ET-1 during 7 or 28 days. After in vivo hemodynamics, the lungs were isolated to derive pressure-flow relations. Small pulmonary arteries ( approximately 250 microm) were mounted on an isometric myograph to study their reactivity. RESULTS: Plasma ET-1 approximately doubled (p < 0.05) after 7 and 28 days. Lung tissue ET-1 level increased fourfold after 7 days (p < 0.001) but was no longer significantly elevated after 28 days. Right ventricular systolic pressure was unaffected. The pulmonary pressure-flow relation shifted upward with a steeper slope (p < 0.05) at 7 days, but not after 28 days. Maximum dilatations to both acetylcholine (p < 0.01) and sodium nitroprusside (p < 0.001) were greatly reduced by approximately 50% after 28 days and were normalized by the addition of the nitric oxide synthase inhibitor L-NNA and the antioxidant N-acetyl-L-cysteine, respectively. CONCLUSION: Chronic hyperendothelinemia reduces the pulmonary vasodilator reserve in response to nitric oxide. Correction by an antioxidant and L-NNA suggests that this relates to increased production of reactive oxygen species, which may have clinical relevance for conditions associated with chronic increase of ET. Further studies are required to determine if, in the long term, this could contribute to the development of pulmonary hypertension.
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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".