ENaC expression correlates with the acute furosemide-induced K+ excretion

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Background: In the aldosterone-sensitive distal nephron (ASDN), epithelial sodium
channel (ENaC)-mediated Na+ absorption drives K+ excretion. K+ excretion depends
on the delivery of Na+ to the ASDN and molecularly activated ENaC. Furosemide
is known as a K+ wasting diuretic as it greatly enhances Na+ delivery to the ASDN.
Here, we studied the magnitude of acute furosemide-induced kaliuresis under various
states of basal molecular ENaC activity.
Methods: C57/Bl6J mice were subjected to different dietary regimens that regulate
molecular ENaC expression and activity levels. The animals were anesthetized and
bladder-catheterized. Diuresis was continuously measured before and after administration of furosemide (2 µg/g BW) or benzamil (0.2 µg/g BW). Flame photometry
was used to measure urinary [Na+] and [K+]. The kidneys were harvested and, subsequently, ENaC expression and cleavage activation were determined by semiquantitative western blotting.
Results: A low K+ and a high Na+ diet markedly suppressed ENaC protein expression, cleavage activation, and furosemide-induced kaliuresis. In contrast, furosemideinduced kaliuresis was greatly enhanced in animals fed a high K+ or low Na+ diet,
conditions with increased ENaC expression. The furosemide-induced diuresis was
similar in all dietary groups.
Conclusion: Acute furosemide-induced kaliuresis differs greatly and depends on the
a priori molecular expression level of ENaC. Remarkably, it can be even absent in
animals fed a high Na+ diet, despite a marked increase of tubular flow and urinary
Na+ excretion. This study provides auxiliary evidence that acute ENaC-dependent K+
excretion requires both Na+ as substrate and molecular activation of ENaC.
TidsskriftPhysiological Reports
StatusUdgivet - jan. 2021

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