Chronic clofibrate administration prevents saline-induced endothelial dysfunction and oxidative stress in young Sprague-Dawley rats
Bibliographic record
Abstract
PURPOSE: High salt intake causes hypertension and endothelial dysfunction in young Sprague-Dawley rats. Clofibrate (clof) prevents this salt induced hypertension. We asked whether clof can prevent salt-induced endothelial dysfunction, and if so, its mechanism. We also questioned whether high salt intake can induce endothelial dysfunction without hypertension in older animals. METHODS: Young (Y, 5 weeks) and old (O, 53 weeks) male Sprague-Dawley rats were given either vehicle (Con, 20 mM Na2CO3) or 0.9% NaCl (Sal) to drink for three weeks. Some young rats received clof (80 mg/d) in their drinking fluid. After three weeks, we measured mean arterial pressure (MAP), endothelial function, by comparing hypotensive responses to acetylcholine (ACh, endothelium dependent) and sodium nitroprusside (SNP, endothelium independent), plasma total nitrite+nitrate levels (PNOx), by the Griess reaction, and aortic superoxide production by lucigenin chemiluminescence. RESULTS: Carotid artery MAP did not change in O. Sal-Y developed hypertension: 133+/-3 vs. 114+/-2 mmHg, P < 0.001, which was prevented by clof: 105+/-2 mmHg. ACh induced a similar dose dependent hypotensive response in Con-O and Sal-O that was inhibited by L-NAME (100mg/kg i.v.). Responses to ACh were blunted in Sal-Y but not in Con-Y. Further, L-NAME inhibited ACh responses only in Con-Y. The response to SNP was similar in all animals. Importantly, the ACh-induced hypotensive response was potentiated in clof+Sal-Y, an effect which was attenuated by blocking calcium-activated potassium channels (KCa) with a combination of apamin (50 ug/kg i.v.) + charybdotoxin (50 ug/kg i.v.), but not by L-NAME. PNOx was reduced in Sal-Y compared to Con-Y (2.09+/-0.26 vs. 4.8+/-0.35 microM, P < 0.001), but not in Sal-O. Aortic superoxide production was higher (P < 0.001) in Sal-Y (2388+/-40 milliunits/mg/min) than Sal-O (1107+/-159 milliunits/mg/min), but was reduced by clof (1378+/-64 milliunits/mg/min; P < 0.001). CONCLUSIONS: High salt intake increases oxidative stress in young animals, leading to impaired nitric oxide activity and endothelial dysfunction. Clofibrate prevents endothelial dysfunction partly through reduced O2 - formation but mainly via selective activation of KCa channels. Older animals are resistant to both salt induced hypertension and oxidative stress.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.003 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".