Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in various models of acute renal failure in rats.
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.
Yao
K
K
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kusaka
H
H
Sano
J
J
Sato
K
K
Karasawa
A
A
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use*
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D005665:Furosemide