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Furosemide Reduces BK‐αβ4‐Mediated K+ Secretion in Mice on an Alkaline High K Diet
Author(s) -
Wang Bangchen,
Sansom Steven
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.620.8
Subject(s) - furosemide , diuretic , nephron , endocrinology , chemistry , medicine , excretion , urine , diuresis , urinary system , kidney
Because of its cardio‐protective benefits, a high K diet is often warranted in conjunction with diuretics such as furosemide for treating hypertension. It is critical to understand how such diets influence the diuretic actions on renal K handling in order to choose the best drug for patients. Studies have shown that furosemide acidifies the urine by increasing acid secretion from thick ascending limb. On the other hand, the Ca 2+ ‐activated large conductance K channel (BK‐αβ4) is regulated by pH. We hypothesized that in mice on an alkaline high K diet (HK), furosemide reduces BK‐αβ4‐mediated K + secretion in the distal nephron by acidifying the urine. To test our hypothesis, HK‐adapted wild‐type (WT) and BK‐β4 knockout mice (β4KO) were given either control water or furosemide water (0.1 g/L). Urine was collected in metabolic cages on the day before treatment and 1, 4, 7, 11, and 14 days after treatment. Mice were then sacrificed to collect blood and kidneys. The urine pH was reduced after furosemide treatment in both WT and β4KO. Urinary K+ excretion was reduced on day 1 of furosemide treatment in WT (2801 ± 235 vs. 2175 ± 119 μmol/day) but not β4KO (1934 ± 497 vs. 2395 ± 207 μmol/day). After 14 days of treatment, renal K + clearance was decreased and plasma [K + ] increased in WT (ctrl water: 591 ± 45 mL/day; 4.46 ± 0.13 mM vs. furo water: 424 ± 32 mL/day; 5.13 ± 0.10 mM) but not β4KO (ctrl water: 453 ± 42 mL/day; 5.04 ± 0.19 vs. furo water: 516 ± 64 mL/day; 5.03 ± 0.06 mM). Additionally, renal K + clearance was positively correlated with urine pH in WT but not β4KO. Western blotting and immunofluorescence staining showed that furosemide decreased total protein expression of BK‐β4 and reduced apical localization of BK‐α. These results indicate that in mice on HK, furosemide reduced BK‐αβ4‐mediated K + secretion by acidifying the urine, making furosemide a K‐sparing diuretic in the setting of an alkaline high K diet. Support or Funding Information This project was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants R01‐DK‐092474, R01‐DK‐071014 and F30‐DK‐108456. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .