Distinct effects of amlodipine treatment on vascular elastocalcinosis and stiffness in a rat model of isolated systolic hypertension
Bibliographic record
Abstract
OBJECTIVE: Medial elastocalcinosis (MEC) contributes to the development of large artery stiffness and isolated systolic hypertension. Since endothelin receptor antagonists can prevent and regress elastocalcinosis, our aim was to determine whether amlodipine, a calcium channel blocker that inhibits endothelin signaling, could likewise influence MEC, or reduce pressure mainly through its vasorelaxing properties. METHODS: Control male Wistar rats were compared with rats receiving warfarin (20 mg/kg per day) with vitamin K1 (15 mg/kg per day) alone (WVK) or in association with amlodipine (15 mg/kg per day) for 4 weeks or during the last week or last 4 weeks of an 8-week WVK treatment (two regression groups). RESULTS: Inactivation of matrix Gla protein by WVK for 4 or 8 weeks increased the calcium content 10-fold in the aorta, inducing a significant elevation of pulse wave velocity and pulse pressure by selective augmentation of systolic blood pressure. Amlodipine prevented aortic MEC, pulse wave velocity and pulse pressure elevation, but reversed only MEC and pulse pressure when administered for 4 weeks. One week of amlodipine administered after 7 weeks of WVK partially decreased pulse pressure without modifying aortic MEC. Amlodipine did not reduce the fibrosis associated with calcified areas in the WVK model during the regression protocols. CONCLUSION: The clinical efficacy of amlodipine in improving hemodynamic variables and reducing cardiovascular events in isolated systolic hypertension could be explained by its beneficial effect on vascular calcification. Amlodipine's lack of effect on pulse wave velocity and collagen deposition, however, suggests that it may reduce pulse pressure by means other than improving arterial stiffness.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".