Abstract 383: Candesartan, in a Dose-Related Manner, Upregulates the Protective Axis of the Renal Renin Angiotensin System and Prevents Progression of Diabetic Nephropathy in db/db Mice.
Bibliographic record
Abstract
The renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cardiovascular and kidney disease. Protection against kidney injury has been evidenced by high dose angiotensin II (Ang II) type 1 receptor (AT1R) blockers. In this study we sought to determine whether a high dose of candesartan has renoprotective actions associated with the modulation of RAS component expression in type 2 diabetic db/db mice. Systolic blood pressure (SBP), urinary albumin excretion (albumin/creatinine, ACR), and protein expression/activity of RAS components were assessed in db/db and control non-diabetic db/+ mice infused with the AT1R blocker candesartan (1, 5, 25, 75 mg/kg/day, sc, 4 weeks). Vehicle treated db/db mice exhibited increased albuminuria (38.9 ± 11.9 ACR) compared with db/+ mice (6.77 ± 1.7 ACR) with no differences in SBP between the two groups (110 ± 9 vs 116 ± 4 mmHg). Candesartan (1 mg/kg/day) had no effect on SBP, although albuminuria was decreased in db/db mice (8.8 ± 3.0 ACR). Candesartan 5 mg/kg/day reduced SBP only in db/+ mice (92 ± 8 mmHg). Diabetic mice receiving 5mg/kg/day showed less albuminuria compared with vehicle treated db/db mice (21.4 ± 6 ACR). Candesartan 25mg/kg/day reduced SBP in both db/db and db/+ mice (77 ± 5 and 76 ± 4 mmHg) and decreased albuminuria in db/db mice (14.95 ± 6.4 ACR). Reduction in SBP (80 ± 7 mmHg) with no improvement of albuminuria (55.9 ± 6 mmHg) was observed in diabetic mice receiving 75 mg/kg/day candesartan. Histological findings showed that candesartan at low dose, but not at high dose, prevented tubular damage in db/db mice. Candesartan, 1-25 mg/kg/day, increased renal expression of AT2R in db/db mice. Expression of ACE2 and MAS receptor was increased only by candesartan (1 mg) in db/db mice. ACE activity was reduced in plasma and kidney cortex of db/db mice, without effect of candesartan. ACE2 activity was increased by candesartan in plasma (5 mg/kg/day) and kidney cortex (1 mg/kg/day) from db/db mice. These results indicate that low to intermediate doses of candesartan reduce the magnitude of albuminuria and tubular damage in diabetic nephropathy. These effects were not evidenced at a higher dose of candesartan. Such processes may be due to activation of the protective axis (ACE2/MAS/AT2R) of the renal RAS.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".