Diabetes Affects the A1 Adenosine Receptor-Dependent Action of Diadenosine Tetraphosphate (Ap4A) on Cortical and Medullary Renal Blood Flow

Abstract

Diabetes through adenosine A1 receptor (A₁R) and P2 receptors (P2Rs) may lead to disturbances in renal microvasculature. We investigated the renal microvascular response to Ap₄A, an agonist of P2Rs, in streptozotocin-induced diabetic rats. Using laser Doppler flowmetry, renal blood perfusion (RBP) was measured during infusion of Ap₄A alone or in the presence of A₁R antagonist, either DPCPX (8-cyclopentyl-1,3-dipropylxanthine) or 8-cyclopentyltheophylline (CPT). Ap₄A induced a biphasic response in RBP: a phase of rapid decrease was followed by a rapid increase, which was transient in diabetic rats but extended for 30 min in nondiabetic rats. Phase of decreased RBP was not affected by DPCPX or CPT in either group. Early and extended increases in RBP were prevented by DPCPX and CPT in nondiabetic rats, while in diabetic rats, the early increase in RBP was not affected by these antagonists. A₁R mRNA and protein levels were increased in isolated glomeruli of diabetic rats, but no changes were detected in P2Y₁R and P2Y₂R mRNA. Presence of unblocked A₁R is a prerequisite for the P2R-mediated relaxing effect of Ap₄A in nondiabetic conditions, but influence of A₁R on P2R-mediated renal vasorelaxation is abolished under diabetic conditions.