Evaluation of Luminal Endothelin-Converting Enzyme Activity in the Pulmonary and Coronary Circulations
Bibliographic record
Abstract
The endothelin-converting enzymes are distributed on both the surface of the endothelium and intracellularly. Whether circulating big-endothelin-1 can be hydrolyzed in plasma by lumen-bound endothelin-converting enzymes is unknown. The lung is the major site for hydrolysis of angiotensin-I to angiotensin-II by the angiotensin-converting enzyme; because of its high content in endothelin-converting enzymes, we hypothesized that the lung could similarly hydrolyze circulating big-endothelin-1. Since big-endothelin-1 produced by the lung can modulate coronary vascular tone, the heart may also have the capacity to hydrolyze circulating big-endothelin-1. Isolated lungs and hearts from Sprague-Dawley rats were perfused at 10 mL/min. Clearance of trace doses of human I125big-endothelin-1 was quantified using the indicator-dilution curves technique with labeled albumin as a vascular reference. Single-pass hydrolysis was assessed by bolus injection of human big-endothelin-1 (24 fmol) followed by serial ELISA determinations of big-endothelin-1 and endothelin-1 levels in effluent samples. To exclude possible uptake of produced endothelin-1, 10(-6) M BQ788 was added to the perfusate. The injections had no effect on perfusion pressures. There was no detectable clearance of I125big-endothelin-1 in the lung; however the heart extracted 14 +/- 1% of the injected tracer. There was no detectable big-endothelin-1 hydrolysis in the pulmonary as well as in the coronary circulations. The pulmonary circulation does not clear or hydrolyze circulating big-endothelin-1 suggesting that endothelin-converting enzymes are predominantly used for intracellular and/or abluminal conversion of locally produced big-endothelin-1. Mild coronary uptake of big-endothelin-1 suggests that this circulating peptide could modulate coronary vascular tone.
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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 | 0.009 | 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 | 0.000 |
| 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".