Canagliflozin produces a vasorelaxation effect on isolated rat thoracic aorta via NO/cGMP pathways
Bibliographic record
Abstract
Abstract Canagliflozin is a sodium-glucose cotransporter 2 inhibitor (SGLT2i) an oral hypoglycemic agent. The present study was performed to determine the vasorelaxant response of canagliflozin along with the underlying mechanism. In diabetes-associated complications, those involving blood vessels remain a high cause of morbidity. The diabetes-related cardiovascular complications should be treated with newer drugs that could cure both complications concurrently. The study was conducted on the aortic rings of Wistar rats of either sex. Canagliflozin (10-8-10-4 M) induces relaxation in phenylephrine (PE 100 µM) and 80 mM KCl pre-contracted rings significantly in a cumulative manner acquiring endothelium. The canagliflozin mechanism of vasorelaxant was established by incubating endothelium intact aortic rings for 30 minutes before PE with; nitro-L-arginine methyl ester (L-NAME 100 µM), methylene blue (10 µM), barium chloride (BaCl2: 10 µM), glibenclamide (1 µM) and indomethacin (10 µM). To estimate the role of calcium (Ca+ 2), cumulative Ca2+ (0.01- 10.0 mM) was added in a bath containing Ca+ 2 free Krebs-Henseleit solution. It was repeated by pre-incubating strips with nifedipine (1 µM) and canagliflozin (1 µM, 10 µM and 100 µM) respectively. The relaxant response of canagliflozin involves the release of nitric oxide, cyclic guanosine monophosphate, prostacyclin, and membrane hyperpolarization from endothelium as pretreatment with L-NAME (IC50: 2.166 × 10− 7 ± 7 M ), methylene blue (IC50 : 1.738 × 10− 7 ± 7 M), indomethacin (IC50: 2.269 × 10− 7± 7 M), BaCl2 (IC50 : 3.320 × 10− 6 ± 7 M) and glibenclamide (IC50: 3.960 × 10− 7 ± 7 M) diminished the response. Additionally, canagliflozin relaxing effects include both decreased Ca+ 2 influx and release from sarcoplasmic reserves. Thus, canagliflozin is a possible adjuvant in diabetes with concurrent hypertension.
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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 | 0.001 |
| 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 | 0.000 |
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".