Abstract 340: Deletion of Cyp2c44-epoxygenase in the Collecting Duct Causes the Hypertension in Mice on a High K Diet
Bibliographic record
Abstract
Previous studies demonstrated that high K (HK) intake caused hypertension in Cyp2c44 (-/-) mice. In the present study we examined the role of Cyp2c44 in the collecting duct (CD) in blood pressure (BP) regulation during increased K intake in a CYP2c44 CD-specific conditional knockout mice (KO). CD specific KO mice were generated by crossing Cyp2c44(flx/flx) mice (a generous gift of from D. Zeldin, MD) with a Hoxb7-Cre+ mice. The KO mice have normal body development and show no visible differences when compared to wt mice. However, increasing dietary K intake from 1% to 4% significantly increased the BP of KO mice (from 125 mmHg to 148 mmHg) but, not that of wt mice. In contrast, feeding KO mice with high salt (4% or 8%) had no significant effect on their BP (126 mmHg). A high (HK) intake also slightly but significantly increased plasma Na concentration of KO mice from 149 mM to 150.3 mM. Moreover, single tubule-real-time PCR experiments demonstrated that a HK intake increased the expression of Cyp2c44 mRNA by 10 folds in the distal convoluted tubule (DCT) but only had a modest effect in the TAL and no effect on Cyp2c44 expression in proximal tubules. Thus, a HK intake is still able to stimulate Cyp2c44 expression in the DCT. Because administration of amiloride decreased the BP of the KO mice on a HK diet to 117 mmHg, we speculate that defective regulation of ENaC by the Cyp2c44 epoxygenase may be responsible for the HK intake-induced hypertension in the KO mice. This speculation was confirmed by patch-clamp experiments performed in the isolated CD of the KO mice. Application of arachidonic acid (AA) inhibited ENaC in the wt mice but failed to inhibit Na channels in the KO mice. However, adding 11,12-EET inhibited ENaC in both wt and KO mice. We conclude that the CD Cyp2C44-epoxygenase in is essential for suppressing ENaC activity in the CD and for preventing hypertension in response to a HK intake.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".