Dataset Information

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

ABSTRACT:

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, furosemide-induced 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.

SUBMITTER: Ayasse N

PROVIDER: S-EPMC7788322 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Ayasse Niklas N Berg Peder P Leipziger Jens J Sørensen Mads Vaarby MV

Physiological reports 20210101 1

<h4>Background</h4>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 mol ...[more]

PMID: 33410279

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