Abstract 12265: Normalization of Renal AT1 Receptor Expression is Observed With Enalapril But Not Diltiazem in a Rat Model of Chronic Kidney Disease
Bibliographic record
Abstract
Introduction: Use of ACE inhibitors (ACEi) improves outcomes in patients with proteinuric chronic kidney disease (CKD) and is considered first line of treatment in recent guidelines. In addition to renin angiotensin (Ang) system blockers, other antihypertensive agents such as calcium channel blockers (CCBs) achieve similar therapeutic effectiveness in renoprotection. Our objective was to determine the impact of antihypertensive therapy on renal Ang type 1 receptor (AT 1 R) in 5/6 subtotal nephrectomy (Nx) rat model of CKD using PET imaging. Methods: Ten weeks after Nx, Sprague-Dawley rats (n=6-8/group) were administered 10mg/kg/d enalapril (NxE), 30 mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional ∼10 weeks. Systolic blood pressure (SBP), plasma creatinine, urine albumin, plasma and tissue Ang II were measured at the end. AT 1 R was assessed using in vivo [ 18 F]FPyKYNE-losartan PET and in vitro autoradiography. Heart function was evaluated with echocardiography. Results: Compared to shams, Nx rats exhibited higher SBP that was reduced by both enalapril and diltiazem (142.7±2, 188.8±17.3, 152±8.7 and 145.8±5.8 mm Hg in sham, Nx, NxE and NxD, respectively, p <0.05). At ∼20 weeks, plasma creatinine and albuminuria were significantly increased in Nx rats, while no changes occurred in NxE rats compared to shams. By contrast, NxD rats demonstrated further increases in these parameters, compared to Nx alone ( p <0.05). Plasma and kidney Ang II were raised in Nx rats, lowered by enalapril and increased significantly in NxD rats ( p <0.05). PET kidney AT 1 R level decreased in Nx rats compared to shams and only enalapril treatment normalized AT 1 R expression (2.8±0.5, 2±0.3, 2.9±0.6, 1.9±0.5 ml/cm 3 in sham, Nx, NxE and NxD respectively, p <0.05) and was confirmed by in vitro results. Enhanced echo LV mass in Nx rats was not reversed by enalapril but was further increased with diltiazem ( p <0.001). Conclusions: In rats with CKD, delayed treatment with the ACEi enalapril normalized AT 1 R expression and reduced progression of the disease, whereas the CCB diltiazem exacerbated renal and cardiac dysfunctions. [ 18 F]FPyKYNE-Losartan PET allows longitudinal determination of AT 1 R abnormalities with progression of cardiorenal failure and monitoring of therapy.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".