Renal vasculature reactivity to agonist of P2X7 receptor is increased in streptozotocin-induced diabetes

BackgroundDiabetic nephropathy is characterized by the dysfunction of renal microvasculature. The involvement of the P2X7 receptor, being a part of the purinergic system, is presumable in this process. The aim of our study was to investigate the P2X7 receptor-mediated renal microvasculature response and renal metabolism of extracellular adenine nucleotides in diabetic rats.MethodsStudy was performed on streptozotocin-induced diabetic Wistar rats. The vascular response to BzATP, an agonist of the P2X7 receptor, was monitored based on the changes of cortical blood flow (CBF), glomerular filtration rate (GFR) and glomerular inulin space (GIS). The renal interstitial fluid (RIF) was probed by microdialysis technique and concentrations of ATP and adenosine were measured. Activity on NTDPase and 5′-nucleotidases was measured on renal membranes.ResultsDiabetic kidneys were characterized by decreased ATP RIF and increased adenosine RIF concentrations with accompanied enhancement of NTDPase and 5′-nucleotidase activities. BzATP induced a more pronounced increase of CBF and decrease of GFR and GIS in diabetes rats. These effects were abolished by A438079, an antagonist of the P2X7 receptor.ConclusionsIt is possible that increased P2X7 receptor reactivity may be involved in the pathogenesis of diabetic nephropathy.