title: The effects of adenosine A2B receptor inhibition on VEGF and nitric oxide axis-mediated renal function in diabetic nephropathy.
abstract: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. The pathophysiologic mechanisms of diabetic nephropathy are incompletely understood but include overproduction of various growth factors and cytokines. Upregulation of vascular endothelial growth factor (VEGF) is a pathogenic event occurring in most forms of podocytopathy; however, the mechanisms that regulate this growth factor induction are not clearly identified. A2B receptors have been found to regulate VEGF expression under hypoxic environment in different tissues. One proposed hypothesis in mediating diabetic nephropathy is the modulation of VEGF-NO balance in renal tissue. We determined the role of adenosine A2B receptor in mediating VEGF overproduction and nitrite in diabetic nephropathy. The renal content of A2B receptors and VEGF was increased after 8 weeks of diabetes induction. The renal and plasma nitrite levels were also reduced in these animals. In vivo administration of A2B adenosine receptor antagonist (MRS1754) inhibited the renal over expression of VEGF and adverse renal function parameters. The antagonist administration also improved the kidney tissue nitrite levels. In conclusion, we demonstrated that VEGF induction via adenosine signaling might be the critical event in regulating VEGF-NO axis in diabetic nephropathy.
authors.affiliation: Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology , Anand, Gujarat , India and.
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.forename: Aswin
authors.initials: A
authors.lastname: Thaker
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D012598:Sclerosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009569:Nitric Oxide
keywords: A2B Adenosine receptor; VEGF; diabetic nephropathy; nitric oxide; streptozotocin