Introduction: Modern diets are high in sodium chloride, which raises blood pressure and has negative health consequences (Hunter et al., 2022). Additionally, dietary potassium intake is often comparatively low. Dietary sodium and potassium have a well-known influence on blood pressure. Interventions that increase potassium intake reduce blood pressure in clinical trials (Filippini et al., 2020), and oral potassium salts were historically used as diuretics (Keith et al., 1935) to reduce extracellular fluid volume and decrease blood pressure. In mice, oral delivery of potassium chloride (KCl), dephosphorylates and deactivates the sodium chloride cotransporter (NCC) of the distal convoluted tubule (Penton et al., 2016). The goal of this study was to evaluate the impact of an acute rise in plasma potassium concentration on sodium excretion and NCC expression in the kidney.

Methods: Male and female Sprague-Dawley rats (n=19) aged 12-15 weeks were anaesthetised (Thiopental sodium 50mg/kg IP). The jugular vein and carotid artery were cannulated, a tracheotomy performed and the bladder catheterised (Ivy et al., 2018). An arterial blood sample was taken for measurement of plasma electrolytes, and rats were then randomised to receive an IV administration of either 140mmol/L NaCl (control) or 140mmol/L KCl at a rate of 1mL/hr/100g body weight. Both solutions also contained 0.25% FITC-inulin (for determining glomerular filtration rate; GFR) and 10mmol/L Na-aminohippurate (for measurement of renal plasma flow; RPF). After 1 hour, urine was collected for a 60-minute period, with a second arterial blood sample.  Rats were then euthanised through anaesthetic overdose, and the left kidney was removed for western blot analysis of total NCC (tNCC) and T53-phosphorylated NCC (pNCC) expression.

Results: Outputs from male and female rats were pooled for analysis; comparisons between groups treated with control (NaCl) or KCl infusion were performed using unpaired t-tests, and significance values were set at p<0.05. Results are presented as mean±SD. Plasma sodium, potassium and chloride concentrations measured before randomisation were not different between groups. Following 2 hours of infusion, plasma potassium was significantly higher in rats infused with KCl than those treated with an NaCl control (Control: 3.9±0.6mmol/L/ KCl: 5.2±0.9mmol/L; p<0.0001). No significant statistical differences were found in arterial blood pressure, haematocrit, RPF or GFR between groups. Urine flow was significantly higher in the potassium infusion group (Control=10.3±7.9µl/min; KCl=19.3±15.9µl/min; p=0.03) with a higher excretion rate of sodium (p=0.03), potassium (p=0.0014), and chloride (p=0.0014) in males. Pooling both control and KCl-treated rats, correlation between plasma potassium concentration and urinary sodium excretion was not significant. Western blot analysis showed a lower expression of both total NCC (p=0.02) and phospho-NCC (p=0.03), Negative correlation was found between plasma potassium concentration and expression of tNCC (r=-0.55; p=0.02) and pNCC (r=-0.53; p=0.02).

Conclusion: An acute increase in plasma potassium within the physiological range following 2 hours of KCl infusion reduced the kidney expression of total and activated NCC leading to the observed diuretic and natriuretic effects associated with an elevated plasma potassium load. These are preliminary findings, and the acute effect of increasing plasma potassium on extracellular fluid volume balance has to be studied further.