#681 Blood pressure modulation through altered epithelial sodium channel (ENaC) expression induced by microbiome exchange between Milan normotensive and hypertensive rat strains
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Résumé
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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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle