Cyclosporine A and purininergic receptors in rat kidney

Previous reports have demonstrated that Cyclosporine A (CyA) chronically ad ministered induces an increase in adenosine plasma concentration by inhibit ing adenosine uptake by red blood cells (RBC). We hypothesized that this ef fect may modulate, by a down regulation, the m RNA expression of adenosine receptors in rat kidney. Since high blood pressure (HBP) is a classical sid e effect of CyA treatment, nicardipine, a dihydropyridine calcium channel b locker, is often associated with CyA in treatment. To distinguish between t he effects of CyA-induced HBP and the effects of CyA by itself, we have eva luated the effects of CyA and/or nicardipine on the mRNA expression of Al a nd A2a adenosine receptors. The study was performed on five groups of rats (n= 8) receiving during 21 days either serum saline (0.5 mi i.p), CyA (12 m g/kg/day, i.p), nicardipine (1.2 mg/kg i.p) or nicardipine + CyA. The last (or fifth) group was injected with vehicle (0.5ml i.p). Blood samples for a denosine assay were collected in the renal artery at day 21, just before th e rat kidneys were removed for quantitation of adenosine Al and A2a mRNA co ncentration by RT-PCR. We make two conclusions :i) Nicardipine induces a de crease in mRNA expression of Al but not of A2a adenosine receptors. However , because nicardipine lowered both blood pressure and A1 mRNA expression, i t is not possible to conclude if Al mRNA decrease is implicated in the nica rdipine effects on blood pressure.ii) CyA induces an increase in renal arte ry adenosine concentration and a decrease in mRNA expression of Al and A2a adenosine receptors.