Diuretic Effects of KW-3902, a Novel Adenosine A1-Receptor Antagonist, in Various Models of Acute Renal Failure in Rats.
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概要
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Using various models of acute renal failure (ARF) in rats, the diuretic effects of 8-(noradamantan-3-yl)-1, 3-dipropylxanthine (KW-3902), a novel adenosine A<SUB>1</SUB>-receptor antagonist (0.01 and 0.1 mg/kg, p.o.), were determined and compared with those of furosemide (30 mg/kg, p.o.) and trichlormethiazide (TCM; 1 mg/kg, p.o.). In cisplatin-induced ARF rats, KW-3902 and TCM, but not furosemide, increased Na excretion. KW-3902 did not affect creatinine clearance (CORE), while TCM decreased C<SUB>CRE</SUB>. In gentamicin-induced ARF rats, KW-3902 increased urine volume (UV) and Na excretion. In glycerol-induced oliguric ARF rats, KW-3902, but not furosemide or TCM, increased UV, Na and K excretion and tended to improve the depressed C<SUB>CRE</SUB>, suggesting that the improvement of renal hemodynamics might also contribute to the diuretic effect of KW-3902. In glycerol-induced polyuric ARF rats, only KW-3902 significantly increased UV and Na excretion. These results demonstrate that KW-3902 induces natriuretic effects in various models of ARF and that the effect of KW-3902 is more prominent than those of furosemide and TCM. The present results suggest that endogenous adenosine may be involved in various forms of ARF via adenosine A<SUB>1</SUB>-receptors.
- 公益社団法人 日本薬理学会の論文
著者
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Yao Kozo
Department Of Pharmacology And Molecular Biology Pharmaceutical Research Center Kyowa Hakko Kogyo Co
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Karasawa Akira
Deparment Of Pharmacology Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Sato Kiyoshi
Department Of Biological And Chemical Engineering Gunma University
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Sano Jun-ichi
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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Kusaka Hideaki
Department of Pharmacology and Department of Toxicology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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Yao Kozo
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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