Department of Clinical Chemistry, Medical University of Gdańsk, Gdańsk, Poland.
Department of Molecular Medicine, Medical University of Gdańsk, Gdańsk, Poland.
J Vasc Res. 2021;58(1):38-48. doi: 10.1159/000511461. Epub 2020 Nov 18.
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.
糖尿病可能通过腺苷 A1 受体（A1R）和 P2 受体（P2R）导致肾脏微血管紊乱。我们研究了 P2R 激动剂 Ap4A 对链脲佐菌素诱导的糖尿病大鼠肾脏微血管的反应。使用激光多普勒血流仪，在单独输注 Ap4A 或同时输注 A1R 拮抗剂 DPCPX（8-环戊基-1,3-二丙基黄嘌呤）或 8-环戊基茶碱（CPT）的情况下，测量肾血液灌注（RBP）。Ap4A 在 RBP 中引起双相反应：快速下降阶段后是快速增加阶段，在糖尿病大鼠中是短暂的，但在非糖尿病大鼠中持续 30 分钟。DPCPX 或 CPT 对两组大鼠的 RBP 下降阶段均无影响。DPCPX 和 CPT 可预防非糖尿病大鼠的早期和持续 RBP 增加，但在糖尿病大鼠中，这些拮抗剂对早期 RBP 增加没有影响。糖尿病大鼠分离的肾小球中 A1R mRNA 和蛋白水平增加，但 P2Y1R 和 P2Y2R mRNA 没有变化。在非糖尿病条件下，未阻断的 A1R 是 Ap4A 介导的 P2R 松弛作用的先决条件，但在糖尿病条件下，A1R 对 P2R 介导的肾脏血管舒张的影响被消除。
