1Previous 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 CPX) on the development of ARF.2 In the anaesthetised rat 8-PT (4mgkg-', i.v.) and CPX (O.1mgkg-1, i.v.) antagonised adenosine-evoked responses which are thought to be mediated via Al-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 (O.1 mg kg1, 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 paminohippurate. 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.

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The adenosine antagonist 8-phenyltheophylline (8-PT) is a diuretic in normal rats and can ameliorate glycerol-induced acute renal failure (ARF) in this species. To define which action of 8-PT is important in its salutary effect in ARF, we have compared its effects with those of enprofylline (a xanthine with little affinity for adenosine receptors) and with those of the tubular diuretic hydrochlorothiazide. In one series of experiments, groups of rats with ARF of 24 h duration were given a single dose of drug or vehicle. Only 8-PT enhanced urine volume when compared with the vehicle-treated group. In a second set of experiments, groups of glycerol-injected rats received drug or vehicle treatment (i.p.) twice daily for 2 days. Rats which received a course of 8-PT treatment had significantly lower plasma urea and creatinine concentrations, a higher glomerular filtration rate, a lower kidney weight and improved kidney morphology when compared with vehicle-treated rats. The only beneficial effect noted after enprofylline treatment was an improved kidney morphology. Hydrochlorothiazide treatment compared with vehicle treatment did not ameliorate any index of renal function but resulted in significant elevations in plasma urea and creatinine levels. The inability of enprofylline or hydrochlorothiazide to mimic the effects of 8-PT in ARF indicate that the effects of 8-PT are probably associated with adenosine receptor blockade and not with a tubular diuretic action.