Effects of a selective adenosine A(1) receptor antagonist on the development of cyclosporin nephrotoxicity

被引:4
作者
Balakrishnan, VS [1 ]
vonRuhland, CJ [1 ]
Griffiths, DFR [1 ]
Coles, GA [1 ]
Williams, JD [1 ]
机构
[1] UNIV WALES COLL MED, CARDIFF ROYAL INFIRM, INST NEPHROL, CARDIFF CF2 1SZ, S GLAM, WALES
关键词
adenosine A(1) receptor antagonist; FK453; cyclosporin; nephrotoxicity; glomerular filtration rate; effective renal plasma flow; nifedipine;
D O I
10.1111/j.1476-5381.1996.tb15275.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The clinical application of cyclosporin as an immunosuppressive agent is limited by its nephrotoxicity. 2 The effect of FK453, a selective A(1)-receptor antagonist, administered twice daily to rats at a dose of 100 mg kg(-1) was assessed on the development of nephrotoxicity induced by cyclosporin (10 mg kg(-1) i.p. daily) administered for 14 days. The effects of nifedipine administered twice daily (0.3 mg kg(-1) s.c.) for 14 days, on cyclosporin nephrotoxicity were also studied. 3 Cyclosporin induced a 46.58% and 35.78% decline in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) respectively and a reduction of 16.69% in filtration fraction (FF). Co-administration of FK453 resulted in falls of 30.5%, 18.59% and 14.7% in GFR, ERPF and FF respectively, the former two significantly less than the falls seen with cyclosporin (CyA) alone (P<0.05 vs CyA, ANOVA). 4 Nifedipine appeared to have a more pronounced protective effect resulting in a decline of only 20.91% in GFR, with no significant change in ERPF (increase of 0.93%) when co-administered with CyA. 5 These observations indicate adenosine plays a minor role in the pathophysiology of CyA nephrotoxicity.
引用
收藏
页码:879 / 884
页数:6
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