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

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.