101 PRESERVED VASODILATION VIA ACTIVATION OF PROTEASE-ACTIVATED RECEPTOR-2 IN SHRSP.Z-LEPR FA /IZMDMCR RATS (SHRSP.ZF), AN ANIMAL MODEL OF METABOLIC SYNDROME
Bibliographic record
Abstract
Background: Metabolic syndrome (MetS) is characterized by the accumulation of atherosclerotic risk, which includes insulin resistance, visceral obesity, hypertension, dyslipidemia and systemic pro-inflammation. Expressed in vascular beds, protease-activated receptor-2 (PAR2) has been implicated in the control of vascular tone. Within the blood vessel wall, PAR2 expression was increased by atherosclerosis, and pro-inflammatory cytokines. PAR2 signaling may have greater importance under inflammatory pathological conditions, but the role played by PAR2 in MetS is uncertain. Methods: We therefore examined changes in the vasodilation caused by PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly), in SHRSP.ZF with MetS. We assessed the vasodilation mechanisms involved in the observed functional changes by treatment with inhibitors using myograph methods. Results: At 18 weeks of age, male SHRSP.ZF were not only obese and hypertensive, but also were hyperlipidemic, hyperglycemic, and hyperinsulinemic. Vasodilations of SHRSP.ZF aorta by acetylcholine (ACh) and nitroprusside were less, but vasodilations by 2fly were not different than those of controls (Wistar-Kyoto). In SHRSP.ZF aortas, ACh- and 2fly-induced relaxations were abolished by treatment with a NO synthase inhibitor and a guanylyl cyclase inhibitor. Also in SHRSP.ZF aortas, COX-inhibitors increased ACh-induced relaxations, but did not affect 2fly-induced relaxation. Conclusions: These results demonstrate that SHRSP.ZF aorta vasodilation by PAR2 activation is preserved, even though the mechanism is dependent on NO-cGMP signalling and the evidence indicates NO signalling by other receptors is reduced. These findings suggest that endothelium NO synthesis resulting selectively from activation of PAR2 is enhanced in MetS.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".