Effect of the Selective Adenosine Ai-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.