The Effects of Dietary Potassium on Mouse Blood Pressure and Ion Transport
Authors: Boyd‐Shiwarski Cary , Weaver Claire , Nkashama Lubika , Connolly Kelly , Shiwarski Dan , Mutchler Stephanie , Marciszyn Allison , Subramanya Arohan 
Published: June 2021

For almost a century it has been well appreciated that in humans, dietary potassium intake correlates inversely with blood pressure. Yet, it is unclear how potassium restriction leads to hypertension, and how potassium excess causes a natriuresis despite elevated aldosterone levels. Our goal was to study the effects of dietary potassium in a wild‐type SV129 mouse model to determine the role of K+ in blood pressure, volume regulation, acid/base balance, and ion transport. Mice were fed 4 different diets: low K+ (0.003% K+), normal K+ (0.93% K+), high K+ alkali (5% K+), and high KCl (5% K+) diet for 10 days. Results were obtained using radiotelemetry probes, metabolic cages, and western blots. We found that simply restricting K+ intake had no effect on blood pressure, whereas potassium loading resulted in a progressive ~10 mmHg increase in blood pressure over the 10d feeding period (p ≤ 0.02). To determine whether these effects were dependent on NaCl intake, we challenged mice with 1% saline, added to their drinking water. The K+ restricted mice developed a brisk NaCl‐induced increase in blood pressure (~8 mmHg), whereas potassium loaded mice exhibited no significant change in blood pressure with saline supplementation. Notably, even a limited K+ restricted period of 10d was associated with the development of mild nephrogenic DI in this model, evidenced by polyuria and a decrease in AQP2 expression. This was associated with a specific increase in the expression of sodium transporters in the proximal tubule and distal convoluted tubule, likely the cause of salt sensitivity. The elevated blood pressure on the K+ supplemented diet was consistent with an effect on transport in the aldosterone‐sensitive distal nephron, and correlated with elevated aldosterone levels, increased activation‐associated cleavage of ENaC, and was amiloride‐sensitive. During K+ loading, despite no differences of dietary anionic content on blood pressure, the expression of NHE3 in proximal tubule and pendrin in intercalated cells were differentially regulated by basic and chloride‐rich diets. Collectively, these findings suggest that in our mouse model, the effect of dietary K+ on blood pressure is linked to NaCl intake, due to differential effects of K+ loading and restriction on sodium transport pathways along the entire length of the nephron. In conclusion, standard mouse diets that simply modulate K+ content do not recapitulate the previously reported effects of dietary potassium on blood pressure in humans. Rather, the dietary sodium:potassium ratio as well as the accompanying anionic content should be taken into consideration when modeling the physiologic effect of K+ intake on tubular salt transport and blood pressure.Support or Funding InformationNIDDK R01 DK098145, NIDDK 1K08 DK118211This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.