Renal adaptation to high salt diet requires tubular Na+ secretion through type A intercalated cells

Rafael, C.; Morla, L.; Billiet, J.; Cheval, L.; Lasaad, S.; Placier, S.; Walter, C.; Picard, N.; Crambert, G. C.

doi:10.64898/2026.02.02.702743

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bioRxiv · 10.64898/2026.02.02.702743

Renal adaptation to high salt diet requires tubular Na+ secretion through type A intercalated cells

Rafael, C.·Morla, L.·Billiet, J.·Cheval, L.·Lasaad, S.·Placier, S.·Walter, C.·Picard, N.·Crambert, G. C.

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Abstract

BackgroundIn the context of increased salt intake in the world population, the understanding of the mechanisms that contribute to its correct renal excretion and therefore, avoid variation of blood volume and blood pressure is of major importance. MethodsMolecular, ex vivo microperfusion on isolated tubules, and integrative analysis, was used to identify, characterize and investigate a Na+ secretion pathway in the collecting duct. ResultsIn collecting duct of mice, salt load induced an increase of the type A intercalated cells (AIC) number, an overexpression of the H(Na),K-ATPase type 2 (HKA2) catalytic subunit Atp12a and a stimulation of the bumetanide-sensitive Na+ secretion in isolated and microperfused tubules. Surprisingly, HKA2KO mice fed a high-salt diet exhibit a strong dysregulation of their Na+ and water balance with a pronounced loss of Na+ and fluid, alkalosis, hypokalemia and low blood pressure. This Bartter-like phenotype is due to an over-inhibition of the thick ascending limb (TAL) related to an elevated PGE2 production. ConclusionOur findings establish that activation of Na+ secretion in AIC act as the fine-tuning knob in the regulation of renal Na+ excretion in response to high salt intake. Its absence is overcompensated by an inhibition of the Na+ transport system of the TAL.

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Rafael, C., Morla, L., Billiet, J., Cheval, L., Lasaad, S., Placier, S., Walter, C., Picard, N., Crambert, G. C.. 2026-02-04. Renal adaptation to high salt diet requires tubular Na+ secretion through type A intercalated cells. https://doi.org/10.64898/2026.02.02.702743

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