Influence of Nitric Oxide Synthase Inhibition and Endothelin-1 Receptor Blockade on Acetylcholine-Induced Coronary Artery Contraction In Vitro in Dilated and Ischemic Cardiomyopathies
Bibliographic record
Abstract
The normal dilatory response to acetylcholine (ACH) is reduced in coronary vessels from patients with dilated cardiomyopathy (DCM) and reversed to a contraction in patients with coronary artery disease (CAD) and ischemic cardiomyopathy (ICM). This study investigated the influence of nitric oxide synthase inhibition and endothelin (ET)-1 receptor blockade on the reactivity to ACH of coronary arteries isolated from patients with end-stage congestive heart failure (CHF) associated or not with CAD. Small (approximately 400 microm) epicardial right coronary arteries were isolated from explanted hearts of patients undergoing transplantation for DCM or ICM. Segments were mounted on a wire myograph to record changes in isometric tension. ACH (1 microM) dilated pre-contracted vessels from DCM hearts but contracted pre-contracted vessels from ICM hearts. In the absence of pre-contraction, ACH (10(-9)-3 x 10(-5) M) induced a small contraction of rings from DCM hearts and a larger contraction (p < 0.05) of rings from ICM hearts. N(omega)-nitro-L-arginine (L-NNA, 100 microM), a NO synthase inhibitor, increased (p < 0.05) sensitivity and maximal response to ACH of vessels from DCM hearts only. In the presence of L-NNA, blockade of ET(A) with BQ123 (1 microM) prevented the effects of L-NNA in DCM, whereas blockade of ET(A/B) receptors with bosentan (10 microM) only reduced vascular sensitivity to ACH without significantly reducing the maximal contraction to ACH in DCM. The antagonists had no effects in vessels from ICM hearts. ACH, however, induced similar contractions of vessels without endothelium in DCM and ICM. These results suggest that ACH induces a contraction by stimulating smooth muscle muscarinic receptors. In coronary arteries isolated from DCM hearts, the contraction is regulated by NO and ET-1, whereas these factors seem to have little influence in ICM. This suggests that endothelial muscarinic receptors are either not expressed or uncoupled in ICM hearts.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".