Decreased Diuretic Response to Furosemide in Rats with Acute Hepatic Failure

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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.
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