Chronic High Potassium Diet Decreases Thiazide‐Sensitive Sodium Excretion in High Fat‐Fed Mice

High fat‐fed mice recapitulate several features of the Metabolic Syndrome, including impaired sodium excretion and increased blood pressure. In this model, post‐thiazide sodium excretion is increased compared to low fat‐fed controls, providing evidence that increased Na‐Cl co‐transporter (NCC)‐mediated transport may contribute to both impaired sodium excretion and hypertension in the Metabolic Syndrome. We sought to test whether a chronic, high potassium diet regulates NCC differently in high fat‐fed mice compared to low fat‐fed controls. We fed high fat‐fed mice either a normal (0.7% w/w) or high (5% w/w) potassium diet for 1 week then performed an intraperitoneal injection either vehicle or 30 mg/kg hydrochlorothiazide and collected urine for 4 hours. We then switched the dietary potassium content of both groups and rechallenged the mice with the same drugs. After a washout period, we sacrificed mice for tissue analysis. While on a high potassium diet, post‐thiazide urinary sodium excretion was no different from vehicle and significantly lower than excretion on a normal potassium diet (0.164 +/− 0.024 vs. 0.026 +/− 0.005 μmol/min, normal vs. high potassium diet, respectively; p<0.001). Post‐thiazide potassium excretion was no different on either diet (0.138 +/0 0.017 vs. 0.109 +/− 0.006 μmol/min normal vs. high potassium diet, respective; p = 0.28) and higher than vehicle. Urine flow rate was no different while on either normal or high potassium diet after vehicle or thiazide injection. Membrane preparations of whole kidney lysate blotted for both total and phosphorylated NCC were not significantly different in high fat‐fed mice on a normal vs. high potassium diet. High fat‐fed mice do not demonstrate the high potassium diet‐induced repression of NCC phosphorylation that is well‐documented in low fat‐fed mice, and have detectable, albeit diminished sodium excretion. These data support a role for attenuated repression of the potassium‐NCC axis in engendering impaired sodium excretion and hypertension in this model of Metabolic Syndrome. Support or Funding Information JMN receives support from the NIH (1K08 DK114567‐01). JMN was previously supported by an American Heart Association Postdoctoral Fellowship (16POST27770003). VB receives support from the NIH (1R01 DK091565). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .