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Abstract: FR-PO604

Adaptation to a High-Salt Diet Requires A-Type Intercalated Cell-Dependent NaCl Secretion

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Rafael, Chloe, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
  • Walter, Christine, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
  • Morla, Luciana, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
  • Lasaad, Samia, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
  • Cheval, Lydie, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
  • Crambert, Gilles, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France
Background

The kidney controls the extracellular volume and the blood pressure because of its ability to excrete efficiently Na+ and Cl- ions. We have recently identified a novel pathway that mediates the secretion of Na+ in the collecting duct (Morla, et al. 2016). This system involves A-type intercalated cells (AIC), NKCC1 and the H,K-ATPase type 2 (HKA2), which is known to be able to transport Na+. Here, we investigated the AIC implication in NaCl renal secretion and the physiological relevance of this pathway in vivo. We speculate that this pathway may help the kidney to excrete large amounts of salt when needed.

Methods

Collecting ducts from control kidneys following a normal and a high-salt diet (8% NaCl, HS) were isolated and analyzed by RT-qPCR and immunofluorescence followed by 3-dimensions reconstruction. To assess the physiological relevance of this novel pathway, we placed HKA2 knockout mice (HKA2KO mice) under HS diet.

Results

On isolated collecting ducts, we observe an increase of the total AIC number under HS diet (+10%).This adaptive proliferation of AIC in response to HS diet suggests a relevant role of AIC in NaCl secretion. RT-qPCR reveal that HS diet leads to a 4- and 1.6-fold increase of HKA2 and NKCC1 expressions, respectively. Altogether these results support the role of HKA2 and NKCC1 in mediating the secretion of NaCl in AIC. Under HS diet, HKA2KO mice display increased urine output and water intake associated with a decreased urinary osmolarity compared to control mice. HKA2KO mice also display a decrease of plasma K+ and a hypochloremic metabolic alkalosis. This phenotype, induced by salt load, resembles Bartter syndrome, a salt-losing pathology due to thick-ascending limb dysfunction. Under HS diet, furosemide induces an 80% increased natriuresis in control mice but only a 30% increase in HKA2KO demonstrating that NKCC2 is less functional in HKA2KO mice. We, therefore, propose that the absence of Na+ secretion through HKA2 is compensated by a stronger inhibition of NaCl reabsorption through NKCC2, leading to a mild Bartter-like syndrome.

Conclusion

In conclusion, we demonstrate that AIC participate to the regulation of Na+ balance through the stimulation of the NaCl secretion pathway under HS diet in vivo and we highlight the critical role of HKA2 in the fine adaptation to a HS diet.

Funding

  • Government Support - Non-U.S.