The Natriuretic Response to Acute K+ Intake

Abstract

IntroductionDiets 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.MethodsMice 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: 1Aldosterone 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.ConclusionOur 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.