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

We investigated the effects of KW-3902 (8-noradamantan-3-yl-1,3-dipropylxan thine), a potent and selective adenosine A(1)-receptor antagonist, on lipop olysaccharide (LPS)-induced reduction of urine volume (UV) in anesthetized dogs, in comparison with those of furosemide. LPS was intravenously adminis tered at a dose of 0.5 mg/kg; and the heart rate (HR), systemic blood press ure (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.) amelior ated the LPS-induced decline of UV and RBF. Furosemide (3.2 mg/kg, i.v.) te nded 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 tha t KW-3902 can ameliorate the oliguria and the decrease in RBF during the ea rly phase of LPS-induced shock. Endogenous adenosine may be involved in the endotoxin-induced oliguria via the adenosine A(1)-receptor.