Rho-kinase inhibitors Y-27632 and fasudil prevent agonist-induced vasospasm in human radial artery
Bibliographic record
Abstract
Radial artery (RA) vasospasm remains a potential cause of early graft failure after coronary artery bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. Our aim was to investigate the mechanism of the vasorelaxant effects of Rho-kinase inhibitors (Y-27632 and fasudil) on the human RA. Segments were obtained from 30 patients undergoing coronary artery bypass graft and were divided into 3-4 mm vascular rings. The rings were stimulated with 10(-5) mol/L phenylephrine (PE) by using the isolated tissue bath technique and were relaxed with 10(-6) mol/L acetylcholine. Relaxation responses were recorded for Y-27632 (10(-9)-10(-4) mol/L), fasudil (10(-9)-10(-4) mol/L), and sodium nitroprusside (SNP) (10(-9)-10(-5) mol/L). Y-27632 and fasudil relaxation responses were repeated in either N(G)-nitro-L-arginine (L-NNA), which is a specific endothelial nitric oxide synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which is a guanylate cyclase inhibitor. SNP relaxation responses were repeated in 10(-8) mol/L Y-27632 and 10(-8) mol/L fasudil. Y-27632 and fasudil caused concentration-dependent vasorelaxation in RA rings precontracted with PE, and maximal relaxation (100%) was recorded at the highest concentration used (10(-4) mol/L). The vasorelaxant effects of Y-27632 and fasudil were significantly reduced in the presence of L-NNA and ODQ, and the pD2 values of Y-27632 and fasudil were not changed. The vasorelaxant effects of SNP were significantly increased in the presence of Y-27632 and fasudil, and the pD(2) values of SNP were not changed. These findings indicate that Y-27632 and fasudil caused concentration-dependent vasorelaxation in the RA rings. Because this effect was decreased in a dose-dependent manner by L-NNA and ODQ, the relaxant effects of Y-27632 and fasudil could be due to stimulation by nitric oxide that is being released. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.
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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) | 0.002 | 0.001 |
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".