Influence of clorgyline treatment on chronopharmacology of furosemide in rats

Abstract

Circadian variations in the adrenergic nervous system have been reported to be altered by chronic treatment with clorgyline, a monoamine-oxidase inhibitor. In the present study, the influence of clorgyline on the chronopharmacology of furosemide, a loop diuretic agent, was examined in rats maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Clorgyline (4 mg/kg/day) or its vehicle alone was infused subcutaneously by osmotic minipumps for 14 days. Furosemide (30 mg/kg) was given orally at 12 am [noon (N)] or 12 pm [midnight (M)]. Urine was collected for 8 hours after the agent, and urinary exretions of sodium and furosemide were determined. Urine volume and urinary excretions of sodium and furosemide were significantly greater at 12 N than at 12 M in the vehicle-infused group of rats. However these administration time-dependent changes in the effects of furosemide and its urinary excretion disappeared in the clorgyline-infused animals. These results suggest that the mode of the diurnal variation in the effects of furosemide is altered by chronic treatment with clorgyline. As chronic clorgyline is considered to disturb the adrenergic nervous system, the present findings are compatible with the hypothesis that this system is involved in the mechanism responsible for the time-dependent change in the effects of furosemide.