ACIDIFYING OF URINE AS A FACTOR WHIC INCREASES DIURETIC AND SALURETIC FUROSEMIDE ACTIVITY IN RATS

Abstract

THE AIM of the research is to study saluretic and diuretic activity of furosemide in rats with the acidification of urine with ascorbic acid. MATERIALS AND METHODS. Studies conducted on Wistar rats, Control group of rats, which was in conditions of normal drinking water treatment, daily for about 7 days-long inragastrically injected with 3 ml of tap water, the same amount of 5% aqueous solution of ascorbic acid. After determining the pH of urine were injected subcutaneously with furosemide at a dose of 2 mg / kg. We determined the daily urine output and excretion of sodium and potassium. Quantum-chemical calculations were performed using DFT B3LYP/6-311G * using the program GAMESS. RESULTS. The study showed that in the control group of animals urine pH was 7.2, while in the group receiving ascorbic acid – 6,0. In these conditions, and the diuretic furosemide saluretic activity varied significantly. Introduction of furosemide control group of rats caused an increase in daily urine output of 3.2 times, the excretion of sodium – in 6 times, the excretion of potassium – in 1.9 times. Introduction diuretic on the background of the prior application of ascorbic acid induced significantly greater changes: an increase in daily urine output of 5.6 times, and urinary sodium excretion of more than 11 times, and potassium – in 3.3 times. Quantum-chemical analysis showed that these differences are attributable to the increase of molecular and ionic forms of diuretic decrease in the lumen of renal tubules in acidification of urine. CONCLUSION. In experiments on rats showed increased diuretic and saluretic activity of furosemide in a shift of primary urine pH to the acid side. These results open the possibility for varying the therapeutic dose-tics and regulation of some of its side effects. In addition, offer some prospects for the modification of the molecule of furosemide in order to change the isoelectric point of the drug, which, in turn, should lead to an increase in its diuretic activity.