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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=17437