title: Effects of a selective adenosine A1 receptor antagonist on the development of cyclosporin nephrotoxicity.
abstract: 1. The clinical application of cyclosporin as an immunosuppressive agent is limited by its nephrotoxicity. 2. The effect of FK453, a selective A1-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.
authors.affiliation: Institute of Nephrology, University of Wales College of Medicine, Cardiff.
authors.forename: V S
authors.initials: VS
authors.lastname: Balakrishnan
authors.forename: C J
authors.initials: CJ
authors.lastname: von Ruhland
authors.forename: D F
authors.initials: DF
authors.lastname: Griffiths
authors.forename: G A
authors.initials: GA
authors.lastname: Coles
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D058914:Purinergic Antagonists; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D058914:Purinergic Antagonists; D011720:Pyrazoles; D011725:Pyridines; D014665:Vasodilator Agents; C077100:FK 453; D016572:Cyclosporine; D009543:Nifedipine