#681 Blood pressure modulation through altered epithelial sodium channel (ENaC) expression induced by microbiome exchange between Milan normotensive and hypertensive rat strains
Bibliographic record
Abstract
Abstract Background and Aims Hypertension constitutes a major health problem leading to cardiovascular diseases. Recent studies showed gut microbiome changes in hypertension, suggesting kidney-gut axis in hypertension. A congenic strain of Milan hypertensive (NA) rats with a mutation in α-adducin gene develops hypertension at 3 months age. Our preliminary study revealed diverse expression of renal sodium transporters in NA rats compared with normotensive strain (MN) rats, indicating abnormal renal salt handling in NA rats. Present study aimed at investigating a possible connection between gut microbiome and blood pressure phenotype in these two strains. Furthermore, we evaluated whether exchange of faeces between two strains may transfer phenotypes via gut microbiome, and mechanisms underlying altered phenotypes. Method NA and MN rats were subjected to ‘homogenization (HOM)’ of the microbiome, consisted of exchanges of bedding with faeces, followed by co-housing in the same cage (MN-HOM and NA-HOM groups). For the baseline (BSL) condition, rats were homogenized within the same strain (MN-BSL and NA-BSL). Systolic blood pressure (SBP) was measured every month. Faeces were collected for microbiota metataxonomic analysis using next generation sequencing of 16S ribosome encoding DNA. Expressions of renal sodium transporters were evaluated by westernblot utilizing kidney samples from those rats. Results At 5 months age, MN-HOM showed a significantly enhanced SBP compared to MN-BSL, suggesting that homogenization did have impact on SBP in MN rats. In contrast, there was no difference in the average SBP between NA-BSL and NA-HOM. The SBP of MN-HOM was still significantly lower than both the NA-BSL and NA-HOM groups. Different gut microbiota compositions were observed in the two strains of rats at baseline, and HOM altered both. Westernblot analyses for the screening of the renal sodium transporters possibly associated with the enhanced SBP in MN-HOM revealed the upregulation of a-ENaC in the cortex of MN-HOM with respect to MN-BSL. Putative role of ENaC on enhanced SBP in MN-HOM was further suggested by amiloride challenging on these rats, in which MN-HOM showed a reduction in SBP comparable to MN-BSL after amiloride treatment. Conclusion We have demonstrated that the hypertensive phenotype in NA rats was transferred to MN rats through homogenization, indicating that the intestinal microbiota or metabolites derived therefrom could modulate ENaC in the cortex and eventually modulate SBP. Further studies are underway to identify metabolites from gut microbiota which may modulate ENaC and eventually blood pressure.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".