The effects of A(2B) receptor modulators on vascular endothelial growth factor and nitric oxide axis in chronic cyclosporine nephropathy

INTRODUCTION: To investigate the actions of adenosine A(2B) receptor modulators on VEGF and NO levels in CsA nephropathy. MATERIALS AND METHODS: Nephropathy was induced by administrating 25 mg/kg (s.c) of CsA for 5 weeks. The VEGF and NO levels were measured in kidney tissue. Serum creatinine, creatinine clearance, urinary albumin excretion, blood urea nitrogen, kidney pathology score were measured to assess renal function. The analysis of mRNA expression of A(2B) receptor and VEGF was performed. RESULTS: Administration of CsA for 5 weeks induced adverse renal function. The mRNA expression of VEGF was reduced in renal tissue after 5 weeks of CsA treatment. The renal VEGF and NO levels were also reduced in these animals. In vivo administration of A(2B) adenosine receptor agonist increased renal VEGF which was inhibited by a selective A(2B) AR antagonist (MRS1754) in CsA-treated animals. The increase in VEGF was associated with reversal of adverse renal functions. The effects of A(2B) AR modulators were prominent in CsA-treated animals compared with control animals suggesting CsA treatment may upregulate A(2B) ARs. The mRNA expression of A(2B) AR was increased after 5 weeks of CsA. CONCLUSIONS: A(2B) AR modulators may provide new therapeutic options to retard CsA nephropathy by mediating renal VEGF and NO.