Molecular mechanisms associated to reversion of proteinuria by RAS antagonists in renovascular hypertensive rats (1088.4)
Bibliographic record
Abstract
The present work aimed to compare the effects of monotheraphy versus combined therapy of enalapril and losartan and investigate the mechanisms by which these antihypertensive agents revert proteinuria in 2K‐1C hypertensive rats. To this end, male Wistar rats were subjected to 2K‐1C surgery or sham‐operation (2K). After six weeks, rats were treated with losartan (30mg/Kg/day), enalapril (20mg/Kg/day), losartan+enalapril (20+30mg/Kg/day) or saline by gavage for 14 days. Systolic blood pressure (SBP, mmHg) was higher in 2K‐1C (247±5) than in 2K (129±2, P<0.0001). Losartan (197±6, P<0.05) and enalapril (205±7, n=8, P<0.05) progressively reduced 2K‐1C SBP, with an additional hypotensive effect in the group treated with both drugs (173±16mmHg, P<0.001). Plasma levels of Ang II and TBARS were similar in 2K and 2K‐1C rats and were not changed by the treatments. Albuminuria was remarkably increased in 2K‐1C control rats when compared to 2K control rats. Treatment of 2K‐1C rats with losartan and enalapril similarly reduced albumin excretion when compared to the untreated 2K‐1C. A more pronounced reduction of albuminuria was observed in rats treated with combined therapy. Lucigenin‐derived chemiluminescence was not different in the right and left kidneys of 2K and 2K‐1C rats. Treatments had no effect upon NADPH oxidase activity. The expression of glomerular proteins, including nephrin and podocin, and of proximal tubular protein such as megalin and the Cl/H+ exchanger ClC‐5 were much lower in 2K1C compared to 2K. Treatment with enalapril or losartan partially reverted whereas combined therapy completely restored the expression levels of nephrin and podocin. Taken together, these results suggest that the antiproteinuric effects induced by RAS inhibitors in 2K‐1C rats does not involve inhibition of ROS, but is associated with normalization of the expression of nephrin and podocin in the glomeruli. Grant Funding Source : Supported by FAPESP, CAPES, CNPq, CIHR and Heart and Stroke Foundation of Canada.
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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) | 0.001 | 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 | 0.001 |
| 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".