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Abstract: TH-PO0292

Blood Pressure Modulation Through Epithelial Sodium Channel (ENaC) Alteration Induced by Microbiome Exchange Between Milan Normotensive and Hypertensive Rat Strains

Session Information

Category: Hypertension and CVD

  • 1601 Hypertension and CVD: Basic

Authors

  • Capasso, Giovambattista, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
  • Suzumoto, Yoko, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
  • Silvestri, Cristoforo, Department of Medicine, Faculty of Medicine and School of Nutrition, Faculty of Agricultural and Food Sciences, CRIUCPQ, INAF and Centre NUTRISS, Université Laval,, Québec City, Quebec, Canada
  • Shams, Abbas, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
  • D'Apolito, Luciano, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
  • Villanova, Antonio, Biogem, Biology and Molecular Genetics Institute, Ariano Irpino, Italy
  • Trepiccione, Francesco, Department of Translational Medical Sciences, University of Campania ‘Luigi Vanvitelli’, Naples, Italy
  • Di Marzo, Vincenzo, Department of Medicine, Faculty of Medicine and School of Nutrition, Faculty of Agricultural and Food Sciences, CRIUCPQ, INAF and Centre NUTRISS, Université Laval,, Québec City, Quebec, Canada
Background

Hypertension is a global health problem associated with diabetes, obesity and cardiovascular diseases. Recent studies indicate substantial changes in gut microbiome in hypertensive individuals, therefore suggesting kidney-gut axis. In the present study, we aimed at investigating possible connections between gut microbiome and blood pressure phenotype utilizing a congenic strain of Milan hypertensive (NA) rats and its littermate normotensive strain (MN) rats. We evaluated whether exchange of faeces between two strains may transfer phenotypes via gut microbiome, and mechanisms underlying altered phenotypes.

Methods

NA and MN rats were subjected to ‘homogenization (HOM)’ of the microbiome, consisted of exchanges of bedding with faeces and co-housing (MN-HOM and NA-HOM). For the baseline (BSL) condition, rats were homogenized within the same strain. Systolic blood pressure (SBP) was measured every month. Metataxonomic analysis of faecal samples were performed by next generation sequencing of 16S ribosome encoding DNA. Expressions of sodium transporters were evaluated by immunoblotting utilizing kidney samples from those rats.

Results

At 5 months age, different gut microbiota compositions were observed in the two strains of rats at baseline, and HOM altered both. In addition, MN-HOM showed a significantly enhanced SBP compared to MN-BSL, suggesting that gut microbiome could have impact on SBP in MN rats. In contrast, there was no difference in the average SBP between NA-BSL and NA-HOM. Immunoblotting revealed the upregulation of ENaC in the cortex of MN-HOM with respect to MN-BSL. Finally, MN-HOM showed a reduction in SBP comparable to MN-BSL after amiloride treatment with significantly enhanced urinary sodium excretion.

Conclusion

We have demonstrated that hypertensive phenotype in NA rats was transferred to MN rats through homogenization, indicating that gut microbiota or metabolites derived therefrom could modulate ENaC in the cortex and eventually modulate SBP. Further studies are ongoing to identify metabolites from gut microbiota which may modulate ENaC and eventually blood pressure.

Digital Object Identifier (DOI)