Sodium vs. Potassium: Renal Excretion and Extracellular Fluid Clearance in Saluresis.

Abstract

A long‐term use of diuretics may lead to disturbances of ion homeostasis. Therefore an evaluation of saluretic effect using only cumulative cation excretion is insufficient. Analysis of diuretic effect is based on standard formulas, when ion concentration in blood serum and urinary ion excretion is considered, but our new proposed formula, presented in this investigation, should be taken into account.Experiments were performed on Wistar rats in accordance with Russian and EU guidelines on the use of animals in research. All measurements between groups were compared by the t‐test with Bonferroni correction for multiple comparisons. All values are presented as the mean ± SEM, p<0.05 was considered significant (here vs. control group).To evaluate the effect of the drug during the exact period of time (t=90 min), cumulative urinary ion excretion (E∑ion, μmol) was calculated, summarizing all the urine samples for that time from an animal. New formula for clearance calculation was proposed: Ċion = E∑ion/IonECF*100, where IonECF – ion concentration in extracellular fluid phase. It showed a ration of renal ion excretion to its total content in extracellular fluid phase. All calculations were made per 100 g BW. Based on the previous research the total content of Na+ was considered ‐ 3254 μmol, K+ − 96 μmol. An injection of either V1a‐agonist or Lasix induced enhanced urinary excretion of Na+ and K+ (Golosova et al., 2017). An injection of 0.1 nmol of arginine‐vasotocin (AVT) enhanced urinary excretion of Na+ (208±18 μmol/90 min, p<0.05) and K+ (60±4 μmol/90 min, p<0.05).The analysis of ion serum concentration during 90 min showed serum Na+ concentration decrease following V1a‐agonist injection. AVT after the whole period of drug action showed no change of serum Na+ content. Surprisingly Lasix led to serum Na+ concentration increase (147±1 mM, p<0.05) after 90 min of investigation. Serum K+ concentration stayed at control level following Lasix injection. K+ loss following V1a‐agonist and AVT injection resulted in decrease of serum K+ concentration (3.8±0.1 and 3.9±0.1 mM, consequently, p<0.05).Standard urinary clearance revealed that V1a‐agonist enhanced CK (0.37±0.10 ml/min, p<0.05); AVT and lasix led to double value of CK (0.69±0.10 and 0.66±0.08 ml/min, p<0.05). This standard clearance approach didn't correspond to serum ion concentration shifts.The use of our new formula revealed that decrease of the total content of Na+ in extracellular fluid was around 7% only following an injection of every drug. The loss of renal K+ was 63% following V1a‐agonist injection. The effect AVT or Lasix resulted in 93% and 103% loss of K+ from the total content in extracellular fluid which seemed like an incompatible with life condition. The new used approach helps to predict a tendency of ion blood serum concentration shifts followed saluretic drugs administration. According to obtained data we should take into consideration not only cumulative excretion which is usually used in clinics and laboratories but the new proposed formula to evaluate and predict the postponed effects of saluretic agents.The results of the current study arise a lot of new questions about physiological organization of the system of ion balance maintenance: the capacity of ion depot and the speed of cations extraction from the depot.Support or Funding InformationThe research was carried out within the state assignment of FASO of Russia (theme No. 01201351572), supported in part by RFBR (project No. 14‐04‐01027).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.