THE INFLUENCE OF CIRCADIAN RHYTHMS ON THE DEGREE OF A DIURETIC EFFECT OF FUROSEMIDE IN RATS

Abstract

THE AIM of the investigation was to analyze the question of possible fluctuation of the effect of diuretics, drugs that are also widely used in cardiologic clinics, depending on the circadian biorhythms in rats. MATERIAL AND METHODS. Furosemide was injected intraperitoneally (20 mg/kg) to rats weighing 200-250 g. Effect of the drug following the injection was assessed at 12pm and at 12 am. Diuresis, excretion of Na+ , K+ and creatinine were measured every 6 hours during a day. Then effects of furosemide were investigated in rats, half of which were kept in the dark during 7 hours, and another half – in the light. In the third series of experiments the biorhythms were distorted: the animals were placed in the dark for 12 hours in the daytime, and at night the light was switched on. Part of the animals was given the drug at 12 a.m., the other part – at 12 p.m. RESULTS. The rats given the diuretic at noon had the level of diurnal urination about 40%, and excretion of Na+ about 30% higher, than in the animals given firosemide at midnight. The growth noted took place at night, since no difference in the action of the drug was observed during the first 6 hours after injection. Injection of furosemide to the rats long kept in the dark resulted in the development of diuresis and natriuresis, that were the same 30-40% higher than the action of the drug in the rats kept in the light. Under conditions of the distorted circadian rhythm no differences in the diuretic and natriuretic effects of furosemide were detected, since the fluctuation depending on the circadian rhythm disappeared. At the same time, sharply increased diurnal excretion of Na+ was noted in animals kept in the light over a long period of time and under conditions of distorted biorhythms. It might be explained by stress effects of a continuous exposure to light and of changed circadian rhythms on sodium excretion in nocturnal animals – rats. CONCLUSION. The effects observed appear to be due to the involvement of regulatory properties of epiphysis and suprachiasmic nuclei of the hypothalamus by means of dophamine and melatonin, as well as to changed formation of the sympathetic system and the hypothalamus-hypophysis-adrenals axis.