Effect of the selective adenosine A1-receptor antagonist KW-3902 on lipopolysaccharide-induced reductions in urine volume and renal blood flow in anesthetized dogs.
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 mg/kg; and the heart rate (HR), systemic blood pressure (BP), renal blood flow (RBF) and UV were measured every 15 min for 4 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 min after the LPS injection. Treatment with KW-3902 (1 mg/kg, i.v.) ameliorated the LPS-induced decline of UV and RBF. Furosemide (3.2 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.
Yao
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. kozo.yao@kyowa.co.jp
Ina
Y
Y
Nagashima
K
K
Ohno
T
T
Karasawa
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D009846:Oliguria / Q000139:chemically induced / Q000188:drug therapy*; D058915:Purinergic P1 Receptor Antagonists; D012079:Renal Circulation / Q000187:drug effects*; D014970:Xanthines / Q000627:therapeutic use*
D004232:Diuretics; D008070:Lipopolysaccharides; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D005665:Furosemide