Open AccessRapid development of vasopressin resistance in dietary K+ deficiency
Author(s) -
Lama AlQusairi,
P. Richard Grimm,
Ava M. Zapf,
Paul A. Welling
Publication year - 2021
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00655.2020
Subject(s) - nephrogenic diabetes insipidus , potassium , potassium deficiency , endocrinology , medicine , aquaporin 2 , diabetes insipidus , vasopressin , insulin resistance , sexual dimorphism , chemistry , biology , diabetes mellitus , mechanical engineering , organic chemistry , water channel , engineering , inlet
The association between diabetes insipidus (DI) and chronic dietary K + deprivation is well known, but it remains uncertain how the disorder develops and whether it is influenced by the sexual dimorphism in K + handling. Here, we determined the plasma K + (P K ) threshold for DI in male and female mice and ascertained if DI is initiated by polydipsia or by a central or nephrogenic defect. C57BL6J mice were randomized to a control diet or to graded reductions in dietary K + for 8 days, and kidney function and transporters involved in water balance were characterized. We found that male and female mice develop polyuria and secondary polydipsia. Altered water balance coincided with a decrease in aquaporin-2 (AQP2) phosphorylation and apical localization despite increased levels of the vasopressin surrogate marker copeptin. No change in the protein abundance of urea transporter-A1 was observed. The Na + -K + -2Cl - cotransporter decreased only in males. Desmopressin treatment failed to reverse water diuresis in K + -restricted mice. These findings indicate that even a small fall in P K is associated with nephrogenic DI (NDI), coincident with the development of altered AQP2 regulation, implicating low P K as a causal trigger of NDI. We found that P K decreased more in females, and, consequently, females were more prone to develop NDI. Together, these data indicate that AQP2 regulation is disrupted by a small decrease in P K and that the response is influenced by sexual dimorphism in K + handling. These findings provide new insights into the mechanisms linking water and K + balances and support defining the disorder as "potassium-dependent NDI." NEW & NOTEWORTHY This study shows that aquaporin-2 regulation is disrupted by a small fall in plasma potassium levels and the response is influenced by sexual dimorphism in renal potassium handling. The findings provided new insights into the mechanisms by which water balance is altered in dietary potassium deficiency and support defining the disorder as "potassium-dependent nephrogenic diabetes insipidus."