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Effects of a selective adenosine A 1 receptor antagonist on the development of cyclosporin nephrotoxicity
Author(s) -
Balakrishnan V.S.,
Ruhland C.J.,
Griffiths D.F.R.,
Coles G.A.,
Williams J.D.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15275.x
Subject(s) - nephrotoxicity , effective renal plasma flow , renal function , filtration fraction , nifedipine , adenosine receptor antagonist , renal blood flow , antagonist , endocrinology , medicine , kidney , pharmacology , chemistry , adenosine receptor , receptor , agonist , calcium
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.