Inability to Upregulate Cytochrome P450 4A and 2C Causes Salt Sensitivity in Young Sprague-Dawley Rats
Bibliographic record
Abstract
BACKGROUND: Young Sprague-Dawley rats develop high blood pressure (BP) when exposed to a high salt intake, whereas adult ones generally do not. We investigated the role of renal cytochromes P450 4A (CYP 4A) and 2C (CYP 2C) in maintaining normal BP. METHODS: Young (age 5 weeks) and adult (age 53 weeks) Sprague-Dawley rats were given either 20 mmol sodium carbonate (vehicle for clofibrate) or 0.9% saline to drink for 3 weeks. Some young animals received the peroxisome proliferator activated receptor (PPAR)alpha agonist clofibrate (80 mg daily). We measured tail-cuff and intra-arterial BP, weight change, sodium balance, 20-hydroxyeicosatetraenoic acid (20-HETE) excretion (by high-performance liquid chromatography), and renal expression of CYP 4A and CYP 2C (by real-time reverse transcriptase-polymerase chain reaction). RESULTS: Saline-treated adult animals remained normotensive: systolic BP (SBP) 117 +/- 2 mm Hg v 117 +/- 1 mm Hg in control animals. In contrast, young rats given saline developed increased SBP: 134 +/- 2 mm Hg v 115 +/- 2 mm Hg in control animals (P < . 001). Interestingly, clofibrate lowered SBP to 102 +/- 2 mm Hg in saline-treated young rats but had no effect in control animals (114 +/- 2 mm Hg). Adult rats given saline increased renal expression of CYP 4A and 2C and excreted more 20-HETE. However, young rats given saline showed no induction, and even reduced CYP 4A and 2C, decreased urinary 20-HETE excretion, and retained sodium. Clofibrate increased renal CYP and 20-HETE excretion and prevented sodium retention. CONCLUSIONS: The products of renal CYP4A and 2C, including 20-HETE, aid in excreting salt. Animals that are unable to increase renal 20-HETE formation do not excrete sodium and are prone to hypertension.
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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 | 0.000 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".