Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, China.
Life Sci. 2011 Aug 1;89(5-6):182-7. doi: 10.1016/j.lfs.2011.06.003. Epub 2011 Jun 15.
To investigate the cardiovascular regulatory mechanism of adenosine A(2A) receptor (A(2A)R) in the rostral ventrolateral medulla (RVLM) in acute myocardial ischemic (AMI) rats.
The animal model of AMI was established by ligating the left anterior descending coronary artery (LAD). The A(2A)R expression was examined by immunohistochemistry, western blot and real-time PCR. CGS21680 and SCH58261 (an agonist and antagonist of A(2A)R) were respectively microinjected into the RVLM. In a subgroup of rats, PD98059 (an antagonist of extracellular signal-regulated kinase (ERK1/2)) was microinjected prior to CGS21680 administration. Phosphorylation of ERK1/2 was examined by western blot.
Our results demonstrated that A(2A)R immunoreactive positive neurons, the expressions of protein and mRNA of A(2A)R in the RVLM of AMI group were increased compared with the sham group. Microinjection CGS21680 into the RVLM inhibited mean arterial pressure (MAP) and heart rate (HR) in both AMI and sham groups. The inhibition was significantly greater in AMI group than in sham group. The cardiovascular effects of CGS21680 mentioned above were almost abolished by prior administration of PD98059. The increase of ERK1/2 in the RVLM with the cardiovascular responses was induced by CGS21680 in AMI rats; this effect was also blocked by SCH58261.
This study reveals that the activated A(2A)R in the RVLM underlies the depressor and bradycardiac responses in AMI rats via phosphorylation of ERK1/2 increasing.
探讨嘌呤能受体 A2A 亚型（A2A 受体）在延髓头端腹外侧区（RVLM）对急性心肌缺血（AMI）大鼠心血管调节的作用机制。
结扎大鼠左冠状动脉前降支建立 AMI 模型，通过免疫组化、Western blot 和实时 PCR 检测 RVLM 中 A2A 受体的表达。将 CGS21680（A2A 受体激动剂）和 SCH58261（A2A 受体拮抗剂）分别微量注射至 RVLM，在其中一组大鼠中，在注射 CGS21680 之前预先注射 PD98059（细胞外信号调节激酶 1/2（ERK1/2）的拮抗剂），通过 Western blot 检测 ERK1/2 的磷酸化。
结果显示，与假手术组相比，AMI 组 RVLM 中 A2A 受体免疫反应阳性神经元、A2A 受体蛋白和 mRNA 的表达增加。将 CGS21680 微量注射至 RVLM 可抑制 AMI 组和假手术组大鼠的平均动脉压（MAP）和心率（HR），AMI 组的抑制作用明显强于假手术组。预先给予 PD98059 可几乎消除 CGS21680 对 MAP 和 HR 的抑制作用。CGS21680 可引起 AMI 大鼠 RVLM 中 ERK1/2 的增加，从而产生心血管反应，SCH58261 也可阻断这种作用。
本研究表明，AMI 大鼠 RVLM 中激活的 A2A 受体通过增加 ERK1/2 的磷酸化，介导了降压和心率减慢的反应。
