Diuretic Effects of KW-3902, a Novel Adenosine A1-Receptor Antagonist, in Various Models of Acute Renal Failure in Rats

Abstract

Using various models of acute renal failure (ARF) in rats, the diuretic effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist (0.01 and 0.1 mg/kg, p.o.), were determined and compared with those of furosemide (30 mg/kg, p.o.) and trichlormethiazide (TCM; 1 mg/kg, p.o.). In cisplatin-induced ARF rats, KW-3902 and TCM, but not furosemide, increased Na excretion. KW-3902 did not affect creatinine clearance (CCRE), while TCM decreased CCRE. In gentamicin-induced ARF rats, KW-3902 increased urine volume (UV) and Na excretion. In glycerol-induced oliguric ARF rats, KW-3902, but not furosemide or TCM, increased UV, Na and K excretion and tended to improve the depressed CCRE, suggesting that the improvement of renal hemodynamics might also contribute to the diuretic effect of KW-3902. In glycerol-induced polyuric ARF rats, only KW-3902 significantly increased UV and Na excretion. These results demonstrate that KW-3902 induces natriuretic effects in various models of ARF and that the effect of KW-3902 is more prominent than those of furosemide and TCM. The present results suggest that endogenous adenosine may be involved in various forms of ARF via adenosine A1-receptors.