Decreased Diuretic Response to Furosemide in Rats with Acute Hepatic Failure HUANG Ye KAMIYA Akira HAYASHI Yoshie INUI Kenichi HORI Ryohei 公益社団法人日本薬学会 Journal of pharmacobio-dynamics 0386846X 11 8 583 589 1988-08 Furosemide diuresis is occasionally reduced in cirrhotic patients with ascites. To define this phenomenon, the amounts of water, electrolytes, and furosemide excreted in urine were measured in control and CCl_4-induced acute hepatic failure (AHF) rats. The diuretic action of furosemide (10mg/kg, i.v.) was reduced in AHF rats, accompanied by increased plasma aldosterone concentration and accelerated urinary K^+ excretion rate. Furosemide transiently increased the urinary inulin excretion rate (UV_<IN>) in both control and AHF rats. Then the UV_<IN> quickly returned to the baseline value in control rats, but rapidly dropped below the baseline in AHF rats. To clarify the contribution of aldosterone in these phenomena, AHF rats were adrenalectomized (ADX) and treated with or without exogenous aldosterone. The UV_<IN> in ADX rats given no infusion or a low-dose aldosterone infusion was similar in pattern to that of the control group, but the UV_<IN> in the ADX rats given a high-dose aldosterone infusion showed a pattern similar to that of the AHF rats not adrenalectomized. These findings indicate that an increase in plasma aldosterone concentration is an important factor responsible for the decreased diuretic action of furosemide, along with the reduced glomerular filtration rate. 1988-08 110003636907 AA00704585 ENG NII-ELS 3 Decreased Diuretic Response to Furosemide in Rats with Acute Hepatic Failure HUANG Ye KAMIYA Akira HAYASHI Yoshie INUI Kenichi HORI Ryohei The Pharmaceutical Society of Japan Journal of pharmacobio-dynamics Furosemide diuresis is occasionally reduced in cirrhotic patients with ascites. To define this phenomenon, the amounts of water, electrolytes, and furosemide excreted in urine were measured in control and CCl_4-induced acute hepatic failure (AHF) rats. The diuretic action of furosemide (10mg/kg, i.v.) was reduced in AHF rats, accompanied by increased plasma aldosterone concentration and accelerated urinary K^+ excretion rate. Furosemide transiently increased the urinary inulin excretion rate (UV_<IN>) in both control and AHF rats. Then the UV_<IN> quickly returned to the baseline value in control rats, but rapidly dropped below the baseline in AHF rats. To clarify the contribution of aldosterone in these phenomena, AHF rats were adrenalectomized (ADX) and treated with or without exogenous aldosterone. The UV_<IN> in ADX rats given no infusion or a low-dose aldosterone infusion was similar in pattern to that of the control group, but the UV_<IN> in the ADX rats given a high-dose aldosterone infusion showed a pattern similar to that of the AHF rats not adrenalectomized. These findings indicate that an increase in plasma aldosterone concentration is an important factor responsible for the decreased diuretic action of furosemide, along with the reduced glomerular filtration rate. HUANG Ye Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University KAMIYA Akira Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University HAYASHI Yoshie Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University INUI Kenichi Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University HORI Ryohei Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University