Excess dietary potassium raises blood pressure in male mice by an aldosterone-dependent increase in ENaC

Hypertension is a risk factor for cardiovascular disease. Low dietary potassium (K+) intake is associated with higher blood pressure (BP) and increased activity of the kidney NaCl cotransporter NCC. Increasing dietary K+ can lower NCC activity and reduce BP, but a threshold for beneficial effects of dietary K+ is apparent, with very high K+ intakes associated with higher BP. Here, we examine in male C57Bl/6J mice if an optimal BP-lowering K+ intake window exists and the molecular basis of K+ driven increases in BP. Telemetric BP recordings are performed in mice receiving diets with normal (0.74%) NaCl content and progressively increasing K+ content (0.75% to 5% K+, as KCl) for 5 days. None of the diets examined reduce BP despite lowering NCC activity and above 1.75% K+ intake systolic BP (SBP) is raised, concurrent with higher aldosterone and sodium channel (αENaC) activity. On a high NaCl diet (1.57% Na+), K+-driven increases in αENaC and SBP are absent and high NaCl does not increase SBP. We conclude that the higher BP subsequent to excess K+ intake is aldosterone and ENaC-dependent, and increased dietary K+ is beneficial when Na+ intake is high. Dietary potassium influences blood pressure. This study shows that excess dietary potassium raises blood pressure via enhanced aldosterone driven ENaC activity. Yet, greater dietary potassium is beneficial to blood pressure when salt intake is high.