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Abstract: FR-PO600

Low ENaC Expression Abolishes Furosemide-Induced K+ Excretion

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Ayasse, Niklas, Aarhus University, Aarhus C, Denmark
  • Leipziger, Jens G., Aarhus University, Aarhus C, Denmark
  • Sorensen, Mads Vaarby, Aarhus University, Aarhus C, Denmark
Background

In the collecting duct (CD) ENaC-mediated Na+ absorption drives K+ excretion. Acute K+ excretion is dependent on the regulated delivery of Na+ to the aldosterone-sensitive part of the distal nephron (ASDN) and acute activation of ENaC. Furosemide is considered a K+ wasting diuretic as it greatly enhances Na+ delivery to the ASDN. Here, we study the magnitude of acute furosemide-induced kaliuresis under various states of CD ENaC expression.

Methods

C57/Bl6J mice were subjected to different dietary regimens altering molecular ENaC expression levels. The animals were anesthetized and bladder-catheterized. Diuresis was continuously measured before and after furosemide (2µg/gBW) was administered. Flame photometry was used to measure urinary Na+ and K+ and ENaC expression levels were determined by semi-quantative Western Blotting.

Results

A high K+ and a low Na+ diet greatly increased ENaC protein expression and furosemide-induced kaliuresis. In contrast, furosemide-induced kaliuresis was greatly reduced in animal fed a low K+ diet and absent in animals on a high Na+ diet, conditions with markedly reduced ENaC expression. No significant differences in furosemide-induced natriuresis were found when comparing the dietary groups but it tended to by higher in the low ENaC expressing groups. The furosemide-induced diuresis was similar in all dietary groups.

Conclusion

Acute furosemide-induced kaliuresis differs greatly and markedly 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. This study provides auxiliary evidence that acute CNT/CCD dependent K+ secretion requires both functional and molecular activation of ENaC.

Funding

  • Government Support - Non-U.S.