High Dietary Salt Limits the Ability of High Potassium to Increase Blood Pressure

Hypertension is a major risk factor for cardiovascular disease. High dietary sodium (Na + ) intake contributes to high blood pressure (BP), but dietary potassium (K + ), typically low in the western diet, also modulates BP. In some studies, higher K + intake lowers BP (1), an effect partially explained by a higher plasma K + reducing the activity of the sodium chloride cotransporter NCC in the kidney distal convoluted tubule (2). However, other studies do not always see a beneficial effect of increasing K + intake on BP (3). The aims of this study were to investigate; 1) the mechanisms and potential of increasing dietary K + to lower BP, 2) the effects of combining K + diets with higher Na + intake and 3) the limitations of such an approach. Methods: Initially, male mice were fed diets containing 0.74% NaCl and incrementally increasing percentages of K + (0.75% to 5% K + , as KCl) for 5 days. BP was recorded using telemetry on the last day of each diet and blood and 24 h urine was collected for clinical chemistries and physiological phenotyping. In another cohort, mice were fed a 0.74% NaCl / 0.75% K + diet and switched directly to a 0.74% / 2% K + diet for 5 days with BP recordings. Finally, mice were fed a high Na + diet (4% NaCl) with 0.75% K+ for 5 days, after which they either remained on this diet or K + intake was increased to 2%. BP reported is 12h active phase systolic BP (SBP). Results: On normal Na + intake, incremental increases in K + intake led to SBP increases after 5 days, which were significant from the 1.75% K + diet and above (D= +5.33 ± 1.10 mmHg). A direct switch to a 2% K + intake also increased SBP (D= +5.10 ± 2.5 mmHg). Plasma K + was not significantly different across the diets relative to 0.75% K + , except for a 5% K + intake (D= +1.01 mmol/L). Urine aldosterone excretion increased linearly with K + intake (R 2 =0.98). Renin activity trended down on 2% K + intake, and the aldosterone/renin ratio (ARR) was significantly increased (+98.3 ± 2.5%). On high Na + , no increase in SBP was detected with 2% K + intake (D= -2.35 ± 1.7mmHg, ns); however, plasma K + was significantly increased compared to control (D= +0.43 mmol/L). Urine aldosterone excretion was significantly reduced on high Na + diets compared to normal Na + . Plasma aldosterone showed similar trends, and renin activity was slightly reduced, resulting in low ARR for high Na + intakes. Conclusion: We show that on normal Na + , 5 days K + supplementation significantly increased SBP. Over the period studied, high Na + alone had no significant effect on BP, but in combination with higher K + prevented the K + -associated increase in SBP. These BP effects appear to be driven by aldosterone, which increases with K + intake but is reduced on a high Na + diet. Future studies to examine if moderate K + feeding can prevent the ability of high Na + to increase BP long-term are warranted. (1) Mente, A. et al., N Engl J Med 371, 601-611 (2014) (2) Poulsen, S et al., J Physiol 597, 4451-4464 (2019) (3) Chaudhary, P. et al., J Hum Hypertens 35, 577-587 (2021). Funding for this project is provided by the European Commission through the Horizon framework, MSCA program; project "Hyper K" number 101105368 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.