Abstract
Men dehydrate more than women during prolonged exercise, but the etiology is unclear. We assessed gender specific water homeostasis in C57BL/6 mice, and found that the basal urine osmolality is higher in female than in male mice (2756±278 vs 2420±185 mOsm/kg: mean±SEM). 12 h water deprivation decreased urinary output by 57 % in females and by 52 % in males (osmolality: 3664±244 vs 3468±318 mOsm/kg). Since β‐intercalated cells (ICs) were shown to play a role in body fluid balance (e. g., Gueutin et al, JCI 2013), we studied the water concentrating ability of mice deficient in the B1 subunit of the V‐ATPase (B1‐/‐ mice). Urinary volume was 10 % higher in B1‐/‐ males and 29 % higher in B1‐/‐ females compared to wild type mice (WT). Unexpectedly, urine output in water‐deprived B1‐/‐ mice decreased by 46 % in females compared to only 17 % in males. Western blot and immunofluorescence staining revealed lower AQP2 expression in B1‐/‐ mice of both sexes compared to WTs. While in dehydrated females AQP2 relocated to the apical membrane region of principal cells (PCs), this effect was much less significant in males, consistent with their weaker concentrating ability. Females have a higher IC/PC ratio than males, and B1‐/‐ females have a higher IC percentage than WTs, whereas B1‐/‐ and WT males do not differ. Our data support the idea that ICs are, via the V‐ATPase, involved in body fluid homeostasis in addition to acid/base balance, and that these effects are gender dependent.
Published Version
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