Kozo Yao*, Yasuhiro Ina, Ken Nagashima, Tetsuji Ohno and Akira Karasawa
Drug Development Research Laboratories, Pharmaceutical Research Institute,
Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun,
Shizuoka 411-8731, Japan
*Corresponding author.ﾊﾊFAX:+81-559-86-7430
E-mail: kozo.yao@kyowa.co.jp
Abstract: We investigated the effects of KW-3902 (8-noradamantan-3-yl-1,3-dipropylxanthine),
a potent and selective adenosine A1-receptor antagonist, on lipopolysaccharide
(LPS)-induced reduction of urine volume (UV) in anesthetized dogs, in comparison
with those of furosemide. LPS was intravenously administered at a dose of
0.5ﾊmg/kg; and the heart rate (HR), systemic blood pressure (BP), renal
blood flow (RBF) and UV were measured every 15ﾊmin for 4ﾊh. Administration
of LPS continuously decreased HR, BP, RBF and UV. KW-3902, furosemide or
their corresponding vehicle was given as a bolus injection 5ﾊmin after the
LPS injection. Treatment with KW-3902 (1ﾊmg/kg, i.v.) ameliorated the LPS-induced
decline of UV and RBF. Furosemide (3.2ﾊmg/kg, i.v.) tended to ameliorate
the LPS-induced decline of UV but not RBF, the duration of the effect being
shorter than that of KW-3902. These results suggest that KW-3902 can ameliorate
the oliguria and the decrease in RBF during the early phase of LPS-induced
shock. Endogenous adenosine may be involved in the endotoxin-induced oliguria
via the adenosine A1-receptor.
Keywords: Lipopolysaccharide, Shock, Acute renal failure, Adenosine,
Adenosine A1-receptor antagonism
Copyrightｩ The Japanese Pharmacological Society 2000
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