Amelioration of glycerol-induced acute renal failure in rats by an adenosine A1 receptor antagonist (FR-113453).
A potent adenosine A1 receptor antagonist, FR-113453, was tested for its preventive effect on glycerol-induced acute renal failure in rats. First, the optimum timing of FR-113453 administration was studied. Oral FR-113453 (100 mg/kg) given 1 h before or 5-10 min after glycerol injection produced a significant reduction of the serum creatinine at 24 h (4.3 +/- 0.8 mg/dL [vehicle] vs. 1.4 +/- 0.4 mg/dL [FR-113453], and 4.7 +/- 1.1 mg/dL vs. 1.3 +/- 0.6 mg/dL, respectively, p < 0.001). However, when FR-113453 was given 2 h after glycerol injection, the serum creatinine did not improve. Creatinine clearance at 24 h after the induction of acute renal failure was significantly better in rats given FR-113453 (100 mg/kg) 1 h before glycerol than in rats given vehicle alone (0.08 +/- 0.08 mL/min vs. 0.01 +/- 0.02 mL/min), (p < 0.01). The kidney weight was lower and less severe histologic changes were observed at 24 h in the FR-113453-treated group. Renal blood flow (measured using 85Sr microspheres) did not change at 24 h after glycerol injection (3.0 +/- 0.9 mL/min/g [vehicle] vs. 3.6 +/- 0.9 mL/min/g [FR-113453]), but renal vascular resistance was significantly reduced by FR-113453 (47.9 +/- 37.9 vs. 26.4 +/- 5.2 mm Hg/mL/min/g, p < 0.05). Beta-ATP levels (measured by 31P-magnetic resonance spectroscopy) were reduced in glycerol-induced acute renal failure, with no difference between the vehicle and FR-113453-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishikawa
I
I
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Shikura
N
N
Takada
K
K
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000097:blood; D005990:Glycerol; D007668:Kidney / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D058914:Purinergic Antagonists; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
D058914:Purinergic Antagonists; D011720:Pyrazoles; D011725:Pyridines; C077100:FK 453; D000255:Adenosine Triphosphate; D003404:Creatinine; D000241:Adenosine; D005990:Glycerol