The Natriuretic Response to Acute K ⁺ Intake

Introduction Diets rich in K + are associated with unexplained protection against hypertension. Acute K + intake induces natriuresis and kaliuresis in mammals linked to marked dephosphorylation of renal Na + /Cl ‐ ‐cotransporters (NCC). Reduced activity of NCC increases Na + delivery to the collecting ducts, hypothesized to increase driving force for ENaC‐dependent K + secretion. Here we investigated K + and Na + excretion in mice adapted either to preserve or promote Na + loss. Methods Mice were fed low (0,03%), control (0,2 % ) or high (2%) Na + diet for 25 days. Weekly, mice received gavage of either K + or vehicle. Mice were placed in metabolic cages and urine was collected real‐time. ENaC‐dependence of kaliuresis was assessed by benzamil injections prior to gavage. Results: 1 Aldosterone and cleavage‐products of ENaC were inversely related to dietary Na + content. 2 K + excretion rate was reduced in mice on high Na + diet compared to the other groups. 3 In all dietary groups, K + load induced natiuresis and complete NCC dephosphorylation. However, maximal Na + excretion rate was reduced 80% in Na + ‐restricted and increased 15% in Na + ‐loaded mice. 4 Benzamil prior to K + loading increased natriuresis and decreased kaliuresis. Importantly, benzamil abolished all differences in kaliuresis and natriuresis between the groups. Conclusion Our data suggest that acute K + ‐induced kaliuresis is completely ENaC‐dependent. Maximal K + excretion rates are attenuated when ENaC is pharmacologically blocked or physiologically down regulated. To supply adequate luminal Na + to the connecting tubules and the collecting ducts NCC is dephosphorylated following acute K + load under all dietary Na + regimes. This leads to natriuresis, even in severely Na + restricted animals.