Effect of the Selective Adenosine A₁-Receptor Antagonist KW-3902 on Lipopolysaccharide-Induced Reductions in Urine Volume and Renal Blood Flow in Anesthetized Dogs

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 0.5mg/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 A₁-receptor.