POTASSIUM INDUCED POLYURIA IN RATS: IS THE ALDOSTERONE PARADOX UP TO DATE?

Introduction Aldosterone is a mineralocorticoid produced by the adrenal glands with several physiological functions. The most studied stimulus for aldosterone secretion is the renin‐angiotensin‐aldosterone system (RAAS). Despite the importance of RAAS, the secretion of aldosterone can also be induced independently by an even more powerful stimulus: plasma potassium. It has been shown that a rise of only 0.1 mM of plasma potassium can increase plasma aldosterone by 35%. This rise in aldosterone is important for potassium excretion by the kidney and this does not interfere with sodium handling that happens during RAAS activation. This is known as the aldosterone paradox. Objective In the present study, we investigated the acute effect of potassium load on the kidney's sodium and potassium handling and its correlation with the aldosterone content in the blood. Method Male Holtzman rats (280 to 300 g) received a single intragastric load of a solution with high potassium concentration (3.5 mL of 4.6 M KCl) and were immediately returned to metabolic cages for urine collection at each hour to measure sodium and potassium excretion. Groups of rats were decapitated at 3, 6, 9 or 12 hours after the intragastric load for blood collection. Serum sodium, potassium, and aldosterone were analyzed. Data are shown as mean ± SEM, and statistical significance was determined by unpaired t‐test. Experimental protocols were approved by the Ethics Committee for Animal Care and Use (CEUA 05/2018). Results We found that potassium overload induced severe hyperkalemia in the first 9 hours (8.2±0.7; 7.7±0.7 and 8.3±0.1 mEq/l after 3, 6 and 9 h, vs. control: 4.0±0.1 mEq/l). Serum potassium was near the control 12 hours after the load (5.3±0.2 mEq/l). Potassium excretion increased by over 6‐fold reaching the maximum 6 hours after the load (1.2±0.1 μEq/min, vs. control: 0.2±0.2 μEq/min; p<0.05). Interestingly, at the same time, sodium excretion also raised 6‐fold compared to control (2.1±0.5 μEq/min, vs. control: 0.3±0.04 μEq/min, 6 h after the load, p<0.05), along with a 6‐fold increase in urine output with a peak 6 hour after the load (18±2.8 μL/min after 6h, vs. control: 2.8±0.1 μL/min, p<0.05). Aldosterone raised continuously from the 3rd to 12th hour after the load (173±15, 203±18, 208±27, 252±44 ng/dL after 3, 6, 9 and 12 h, vs. control: 10.6±2.8; p<0.05). Conclusion The present results show that potassium load rapidly (in 3 hours) increases aldosterone in the blood, simultaneously with increases in sodium excretion and urine output. Therefore, potassium alone can promote high urine output even in the presence of aldosterone, which suggests the aldosterone paradox in the presence of hyperkalemia. Support or Funding Information Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .