Chronopharmacological study of furosemide in rats: (II). Influence of beta-adrenoceptor blockade.

We have previously demonstrated a time-dependent variability in the diuretic effect of furosemide in rats. The present study was undertaken to evaluate the influence of beta-adrenoceptor blockade on these time-dependent variations. Furosemide (5 mg/kg) was administered intra-arterially in Wistar rats at 1000 hrs (03HALO) or at 2200 hrs (15HALO) with pretreatment with either propranolol (10 mg/kg) or atenolol (10 mg/kg). Urine was collected for 60 min after furosemide administration and urinary excretion of sodium and furosemide were determined respectively. Propranolol pretreatment abolished the temporal variations observed in urine volume, urinary sodium and furosemide levels during the observation periods. With atenolol pretreatment, however, all these variables were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study. These results suggest that the beta-adrenoceptor-mediated stimuli, which is blocked by propranolol but not by atenolol, is responsible for the time-dependent changes in the diuretic effect of furosemide.