Effect of the Selective Adenosine A_1-Receptor Antagonist KW-3902 on Lipopolysaccharide-Induced Reductions in Urine Volume and Renal Blood Flow in Anesthetized Dogs

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Author(s)

    • Yao Kozo YAO Kozo
    • Drug Department Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
    • OHNO Tetsuji
    • Drug Department Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
    • KARASAWA Akira
    • Drug Department Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.

Abstract

We investigated the effects of KW-3902 (8-noradamantan-3-yl-1, 3-dipropylxanthine), a potent and selective adenosine A<SUB>1</SUB>-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 0.5mg/kg; and the heart rate (HR), systemic blood pressure (BP), renal blood flow (RBF) and UV were measured every 15min for 4h. Administration of LPS continuously decreased HR, BP, RBF and UV. KW-3902, furosemide or their corresponding vehicle was given as a bolus injection 5min after the LPS injection. Treatment with KW-3902 (1mg/kg, i.v.) ameliorated the LPS-induced decline of UV and RBF. Furosemide (3.2mg/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 A<SUB>1</SUB>-receptor.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(3), 310-315, 2000-11-01

    The Japanese Pharmacological Society

References:  29

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008186227
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5586933
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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