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

Abstract

BackgroundIn 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.MethodsC57/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.ResultsA 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.ConclusionAcute 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.