X-Message-Number: 17437
Date: Sat, 1 Sep 2001 05:13:51 -0700 (PDT)
From: Doug Skrecky <>
Subject: adenosine may mediate glycerol-induced renal failure

Citations: 1-3
<1>
Title
  Further characterization of the protective effect of
  8-cyclopentyl-1,3-dipropylxanthine on glycerol-induced acute
  renal failure in the rat.
Source
  Journal of Pharmacy & Pharmacology.  44(2):109-13, 1992 Feb.
Abstract
  In the rat, treatment with the alkylxanthine
  8-cyclopentyl-1,3-dipropylxanthine (CPX) at a dose of 0.1 mg kg-1 antagonizes
  adenosine-induced falls in renal blood flow and reduces the severity of
  glycerol-induced acute renal failure. Treatment of
  glycerol-injected rats with 0.03 mg kg-1 of CPX resulted in
  no significant improvements in a range of indices of renal function. However,
  treatment with 0.1 or 0.3 mg kg-1 doses of CPX did significantly ameliorate
  acute renal failure although there were no significant differences in the
  degree of protection of renal function afforded by these two doses. In
  glycerol-injected rats, 0.1 or 0.3 mg kg-1 CPX administered
  either as a single dose or repeated doses every 12 h for two days did not
  inhibit renal phosphodiesterase. Thus the beneficial effects of CPX can be
  produced by doses that have no effect on renal phosphodiesterase activity
  whereas 0.1 mg kg-1 of CPX has been shown previously to antagonize the
  actions of adenosine. The findings provide further evidence that the
  beneficial effect of CPX in glycerol-induced acute renal
  failure is a consequence of adenosine antagonism and not phosphodiesterase
  inhibition.

<2>
Title
  Amelioration of glycerol-induced acute renal failure in the
  rat with 8-cyclopentyl-1,3-dipropylxanthine.
Source
  British Journal of Pharmacology.  98(3):1066-74, 1989 Nov.
Abstract
  1. Previous studies have shown that 8-phenyltheophylline (8-PT), a
  non-selective antagonist at adenosine A1- and A2-receptors, can ameliorate
  the severity of glycerol-induced acute renal failure (ARF)
  in the rat. In the present study we have examined the effects of an
  antagonist with selectivity for adenosine A1-receptors
  (8-cyclopentyl-1,3-dipropylxanthine, CPX) on the development of ARF. 2. In
  the anaesthetised rat 8-PT (4 mg kg-1, i.v.) and CPX (0.1 mg kg-1, i.v.)
  antagonised adenosine-evoked responses which are thought to be mediated via
  A1-receptors (bradycardia and decrease in renal blood flow). The agonist
  dose-ratio produced by CPX was equal to or greater than that found with 8-PT
  (heart rate and renal blood flow respectively). The hypotensive response to
  adenosine which is predominantly due to A2-receptor activation was also
  antagonised by 8-PT, whereas CPX was a much less effective antagonist of this
  response. 3. Administration of CPX (0.1 mg kg-1, i.v.; twice daily for two
  days) significantly attenuated the increase in plasma levels of urea and
  creatinine, the increased kidney weight and the renal tubule damage observed
  in rats 2 days following induction of ARF with intramuscular
  glycerol injection. In addition treatment with CPX
  significantly enhanced the clearances of inulin and p-aminohippurate. 4.
  After glycerol injection, the mortality rate over 7 days in
  untreated and vehicle-treated rats was 43% and 21% respectively. In contrast,
  all animals treated with CPX survived over the 7 day observation period. 5.
  These results support the suggestion that adenosine is an important factor in
  the development of ARF and indicate that this effect of the purine is likely
  to be mediated via an adenosine A1-receptor.

<3>
Title
  Aminophylline ameliorates glycerol-induced acute renal
  failure in rats.
Source
  Canadian Journal of Physiology & Pharmacology.  61(6):567-71, 1983 Jun.
Abstract
  The effect of aminophylline (theophylline complexed with ethylenediamine) on
  the severity of glycerol-induced myohemoglobinuric acute
  renal failure was examined in rats. In the first series of experiments, one
  group of rats received twice daily injections of aminophylline following the
  induction of acute renal failure, and a second group (controls) received
  twice daily injections of saline. Only one of the aminophylline-injected rats
  but five of the saline-injected rats died during the 3-day follow-up period.
  Moreover, mean serum creatinine was lower in the aminophylline-injected rats
  than in the saline-injected controls on each of the 3 days, demonstrating
  that aminophylline reduced the renal functional impairment. In the second
  series, single injections of aminophylline were given at the time of
  glycerol injections or 3, 6, or 24 h later. As assessed by
  mean serum creatinine during the 3-day follow up, even single injections had
  protective effects if given during the initiation phase (0-3 h after
  glycerol). Since aminophylline dissociates into theophylline
  in biological fluids, and since theophylline is an adenosine-receptor
  antagonist, these observations are consistent with the hypothesis that
  adenosine plays a pathogenic role in myohemoglobinuric acute renal failure in
  rats.

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