Chronopharmacological study of furosemide in rats: (III). Examination in spontaneously hypertensive and Wistar-Kyoto rats.
We have previously reported that a time-dependent variability is observed in the diuretic effect of furosemide in Wistar rats and the adrenergic system is involved in the mechanisms responsible for this phenomenon. The present study was undertaken to examine chronopharmacological profiles of furosemide in two related but different strains of Wistar rats, spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Furosemide (5 mg/kg) was administered intra-arterially in SHR and WKY at 1000 hrs (03HALO) or at 2200 hrs (15HALO). Urine was collected for 60 min after the drug and urinary excretion of sodium and furosemide were determined respectively. In both groups of rats, urine volume and urinary excretion of sodium and furosemide were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study using Wistar rats. The diuretic effects of furosemide in SHR was not different from those in WKY at 1000 hrs (03HALO) or at 2200 hrs (15HALO). These data indicate that the effects of furosemide also vary with a time of administration in SHR and WKY as observed in Wistar rats. In addition, the present study suggest that the mode of the time-dependent changes in the effects of furosemide in SHR, which is reported to have an altered circadian rhythm in the adrenergic system, does not differ from that in WKY rat.
Fujimura
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Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Ebihara
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D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects*; D004334:Drug Administration Schedule; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D007269:Injections, Intra-Arterial; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D005665:Furosemide