Chronic bosentan treatment improves renal artery vascular function in diabetes
Bibliographic record
Abstract
OBJECTIVE: Endothelin-1 (ET-1) has been suggested to play an important role in the pathogenesis of diabetes-induced vascular complications. The primary purpose of the present study was to examine the potential beneficial effects of chronic ET receptor blockade (with bosentan) on vascular function in renal arteries from streptozotocin (STZ)-induced diabetic rats. DESIGN: Wistar rats were divided into four groups: control (C), control bosentan-treated (CB), diabetic (D) and diabetic bosentan-treated (DB). Following 10 weeks of bosentan treatment, vascular responses to norepinephrine (NE), ET-1, acetylcholine (ACh) were determined in vascular segments of renal arteries, both with and without the endothelium denuded, according to the following protocol: (1) a cumulative dose-response curve (DRC) to NE in the absence and presence of the nitric oxide synthase (NOS) inhibitor L-NAME (2) cumulative DRC to ET-1 and (3) cumulative DRC to ACh in precontracted arteries. In addition, plasma ET-1 was assayed and ET-1-like immunoreactivity was determined in vascular tissues by immunohistochemistry. RESULTS: The maximum contractile responses to NE and ET-1 were markedly exaggerated in endothelium-intact renal arteries from untreated D rats while ACh responses were preserved. Arteries denuded of endothelium did not exhibit exaggerated responses to NE or ET-1. L-NAME treatment did not affect responses to NE in arteries with or without endothelium. Strikingly, responses to NE and ET-1 (in arteries with endothelium) were completely normalized following long-term bosentan treatment. In addition, plasma ET-1 levels did not differ between C and D groups. However, renal arteries isolated from the D group exhibited increased ET-1-like immunoreactivity (local ET-1 content). CONCLUSION: These data uncover, for the first time, beneficial effects of mixed ETA/ETB receptor blockade on renal artery vascular function in diabetes. Alterations in the production and/or action of ET-1 may have important implications in the development of vascular dysfunction in experimental diabetes.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".