Hypertension is a primary risk factor for cardiovascular disease and a major driver of disability and premature death. High dietary sodium (Na⁺) intake contributes to high blood pressure (BP), but evidence is mounting that dietary potassium (K⁺), typically low in the western diet, also modulates BP. In some studies, greater K⁺ intake lowers BP (1), an effect partially explained by a higher plasma K⁺ being associated to lower activity of the sodium chloride cotransporter NCC in the distal convoluted tubule of the kidney (2). However, other studies do not always see a beneficial effect of greater K⁺ intake on BP (3). The aim of this study is to investigate the mechanisms and potential of increasing dietary K⁺ intake to lower BP, the effects of combining it with higher salt intake and the limitations of such an approach.

Methods: Initially, two cohorts of male mice were fed diets containing 0.74% NaCl and increasing percentages of K⁺ (0.75% K⁺, 1%, 1.25%, 1.5%, 1.75%, 2%, 2.5% and 5%) each for 5 sequential days. Cohort 1 had BP recorded using telemetry for 24 h on the last day of each diet. Cohort 2 had blood and 24 h urine collected at the same time points for assessment of renal function and electrolyte balance. In another cohort, mice were switched directly from a 0.75% K⁺ to a 2% K⁺ diet. Mice were then fed either a high salt diet (4% NaCl) combined with a 0.75% or 2% K⁺ intake for 15 days. 

Results: Incremental increases in K⁺ intake led to a linear (R²=0.98) increase in 24 h urinary K⁺ excretion, which plateaued at 2.5% K⁺ (0.35±0.05 to 1.19± 0.28 mmol/24h, mean ±SD). Natriuresis was not significantly different across the diets, with the exception of the 5% K⁺ diet where Na⁺ excretion was 33.8±10.6% lower (p=0.014). 24 h urine volume was significantly increased for all dietary K⁺ intakes > 1.75% K⁺. Systolic BP (SBP, active period) for all dietary K⁺ intakes was not significantly different to control (n=7 vs. n=5), with the exception of the 5% K⁺ where SBP increased by 7.16±1.72mmHg (p=0.014). Plasma K⁺ was not significantly different across the diets relative to 0.75%K⁺, until an intake of 2.5% K⁺, after which plasma K⁺ was significantly higher. A direct switch from a 0.75% to 2% K⁺ diet on normal Na⁺ intake led to an increase in SBP of 5.10±2.5mmHg after 5 days (active period, p=0.027). This increase in SBP was not apparent in mice concomitantly receiving a high Na⁺ diet.

Conclusion: This study shows that progressively increasing K⁺ intake on a normal salt diet leads to increased urinary K⁺ excretion, but no changes in plasma K⁺ or BP, until K⁺ intake exceeds 2.5% K⁺. However, a direct jump to a higher dietary K⁺ intake increases BP on normal salt intake, but this effect is attenuated during high salt intake. The molecular mechanisms underlying these responses are under investigation.