Rapid homeostatic effects of oral potassium loading on the kidney

Abstract

A dietary K+ load induces a rapid kaliuresis and natriuresis, which may occur even before plasma K+ and aldosterone (aldo) levels increase. To get insights into underlying molecular mechanisms, we analyzed the effects of K+ loading on plasma ion concentrations, aldo levels, urinary ion excretion, and expression and/or phosphorylation of renal ion transport proteins in mice that received 2% K+ either via their diet or gastric gavage. After high K+ treatment, plasma K+concentrations rose rapidly (15’) followed by a significant rise of plasma aldo (30’). A rapid and sustained kaliuresis as well as rapid but short natriuresis was detectable. Functional changes were accompanied by a rapid and sustained (15’–6h) dephosphorylation of the NaCl co‐transporter (NCC) and a late (6h) up‐regulation of proteolytically activated epithelial sodium channels (ENaC). The rapid effects on NCC were independent from the co‐administered anion. NCC dephosphorylation was also aldo‐independent, as indicated by experiments in aldo‐deficient mice. The observed urinary Na+ loss relates to NCC, since it was markedly diminished in NCC‐deficient mice. Thus, rapid down regulation of NCC and subsequent activation of ENaC are part of the homeostatic adaptation of the kidney to the increased K+ intake. Down‐regulation of NCC likely explains the natriuretic effect of an acute oral K+ load and may improve renal K+ excretion by increasing the amount of intraluminal Na+ that can be exchanged against K+ in the aldo‐sensitive distal nephron.