Amelioration of Glycerol-Induced Acute Renal Failure in Rats by an Adenosine A1Receptor Antagonist (FR-113453)
作者:
IshikawaIsao,
ShikuraNaoto,
TakadaKeiichi,
期刊:
Renal Failure
(Taylor Available online 1993)
卷期:
Volume 15,
issue 1
页码: 1-5
ISSN:0886-022X
年代: 1993
DOI:10.3109/08860229309065565
出版商: Taylor&Francis
关键词: Adenosine;Adenosine antagonist;Glycerol;Myohemoglobinuric acute renal failure;Renal blood flow
数据来源: Taylor
摘要:
A potent adenosine A, 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 using85Sr microspheres) did not change at 24 h after glycerol injection (3.0±0.9 mL/min/g [vehicle] vs. 3.6±0.9 mL/minig [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 by3IP-magnetic resonance spectroscopy) were reduced in glycerol-induced acute renal failure, with no difference between the vehicle and FR-113453-treated groups. These results demonstrate that FR-113453 ameliorates glycerol-induced acute renal failure when administered before or just after glycerol injection, indicating that adenosine has a very important role in the induction of acute renal failure by glycerol.
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