Panjehshahin M R, Munsey T S, Collis M G, Bowmer C J, Yates M S
Department of Pharmacology, University of Leeds, UK.
J Pharm Pharmacol. 1992 Feb;44(2):109-13. doi: 10.1111/j.2042-7158.1992.tb03572.x.
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.
在大鼠中,以0.1毫克/千克的剂量用烷基黄嘌呤8-环戊基-1,3-二丙基黄嘌呤(CPX)进行治疗,可拮抗腺苷引起的肾血流量下降,并减轻甘油诱导的急性肾衰竭的严重程度。用0.03毫克/千克的CPX治疗注射甘油的大鼠,一系列肾功能指标均未得到显著改善。然而,用0.1或0.3毫克/千克剂量的CPX进行治疗确实显著改善了急性肾衰竭,尽管这两种剂量对肾功能的保护程度没有显著差异。在注射甘油的大鼠中,以0.1或0.3毫克/千克的CPX单次给药或以每12小时重复给药两天的方式给药,均未抑制肾磷酸二酯酶。因此,CPX的有益作用可以由对肾磷酸二酯酶活性无影响的剂量产生,而先前已证明0.1毫克/千克的CPX可拮抗腺苷的作用。这些发现进一步证明,CPX在甘油诱导的急性肾衰竭中的有益作用是腺苷拮抗作用的结果,而非磷酸二酯酶抑制作用的结果。