Abstract
Men tend to dehydrate more than women after prolonged exercise, possibly due to lower water intake and higher perspiration rate. Women are prone to exercise-associated hyponatremia, primarily attributed to the higher water consumption causing hypervolemia. Since aquaporin-2 (AQP2) water channels in the kidney collecting duct (CD) principal cells (PCs) are involved in maintaining water balance, we investigated their role in sex-dependent water homeostasis in wild-type (WT) C57BL/6 mice. Because CD intercalated cells (ICs) may also be involved in water balance, we also assessed the urine concentrating ability of V-ATPase B1 subunit-deficient (Atp6v1b1-/-) mice. Upon 12-hour water deprivation, urine osmolality increased by 59% in WT female mice and by only 28% in males. This difference was abolished in Atp6v1b1-/- mice, in which dehydration induced a ~30% increase in urine osmolarity in both sexes. AQP2 levels were highest in WT females; female Atp6v1b1-/- mice had substantially lower AQP2 expression than WT females, comparable to the low AQP2 levels seen in both Atp6v1b1-/- and WT males. After dehydration, AQP2 relocates towards the PC apical pole, especially in the inner stripe and inner medulla, and to a greater extent in WT females than in WT males. This apparent sex-dependent concentrating advantage was absent in Atp6v1b1-/- females, whose reduced AQP2 apical relocation was similar to WT males. Accordingly, female mice concentrate urine better than males upon dehydration due to increased AQP2 expression and mobilization. Moreover, our data support the involvement of ICs in water homeostasis, at least partly mediated by V-ATPase, in a sex-dependent manner.
Highlights
Water is the largest single contributor to human body mass, ranging from 50 to 60% in an average adult
Atp6v1b1-/- mice revealed no sex-dependent difference, but for both sexes urine osmolality trended towards lower values than those seen in their WT counterparts (Fig 2A)
We show that that female mice concentrate urine better than their male WT animals upon dehydration, and that AQP2 is differentially expressed and regulated in a sex-dependent manner in the kidney
Summary
Water is the largest single contributor to human body mass, ranging from 50 to 60% in an average adult. Men dehydrate more than women after prolonged exercise [1], possibly due to a slightly lower water intake in men, to an increased rate of perspiration, or a combination of both [1]. The mechanism behind exercise-associated hyponatremia (EAH) after endurance training is not well understood. It can be caused by loss of solutes (Na+ and K+) or by retaining excess total body water content, or a combination of both. One of the major risk factors in EAH is excessive water intake, with women being more prone to developing this potentially fatal condition [1, 2, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
