Teng Bunyen, Tilley Stephen L, Ledent Catherine, Mustafa S Jamal
Department of Physiology & Pharmacology, West Virginia University, Morgantown, West Virginia
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Physiol Rep. 2016 Jun;4(11). doi: 10.14814/phy2.12818.
Bolus injections of adenosine and the A2A adenosine receptor (AR) selective agonist (regadenoson) are used clinically as a substitute for a stress test in people who cannot exercise. Using isolated tissue preparations, our lab has shown that coronary flow and cardiac effects of adenosine are mostly regulated by the AR subtypes A1, A2A, and A2B In this study, we used ultrasound imaging to measure the in vivo effects of adenosine on coronary blood flow (left coronary artery) and cardiac function in anesthetized wild-type, A1 knockout (KO), A2AKO, A2BKO, A3KO, A1, and A3 double KO (A1/3 DKO) and A2A and A2B double KO (A2A/2B DKO) mice in real time. Echocardiographic and Doppler studies were performed using a Visualsonic Vevo 2100 ultrasound system. Coronary blood flow (CBF) baseline data were obtained when animals were anesthetized with 1% isoflourane. Diameter (D) and velocity time integral (VTI) were measured on the left coronary arteries (CBF = ((π/4) × D(2) × VTI × HR)/1000). CBF changes were the highest within 2 min of injection (about 10 mg/kg). Heart rate, cardiac output, and stroke volume were measured by tracing the left ventricle long axis. Our data support a role for the A2 AR in CBF and further support our conclusions of previous studies from isolated tissues. Adenosine-mediated decreases in cardiac output and stroke volume may be A2B and/or A3 AR-mediated; however, the A1 and A2 ARs also play roles in overall cardiac function. These data further provide a powerful translational tool in studying the cardiovascular effects of adenosine in disease states.
腺苷推注以及A2A腺苷受体（AR）选择性激动剂（瑞加腺苷）在临床上被用作无法进行运动的人群进行压力测试的替代方法。利用离体组织制剂，我们实验室已表明，腺苷对冠状动脉血流和心脏的作用主要由AR亚型A1、A2A和A2B调节。在本研究中，我们使用超声成像实时测量腺苷对麻醉的野生型、A1基因敲除（KO）、A2A基因敲除、A2B基因敲除、A3基因敲除、A1和A3双基因敲除（A1/3 DKO）以及A2A和A2B双基因敲除（A2A/2B DKO）小鼠的冠状动脉血流（左冠状动脉）和心脏功能的体内效应。使用Visualsonic Vevo 2100超声系统进行超声心动图和多普勒研究。当动物用1%异氟烷麻醉时获取冠状动脉血流（CBF）基线数据。在左冠状动脉上测量直径（D）和速度时间积分（VTI）（CBF = [（π/4）×D²×VTI×心率]/1000）。注射后2分钟内CBF变化最大（约10mg/kg）。通过追踪左心室长轴测量心率、心输出量和每搏量。我们的数据支持A2 AR在CBF中的作用，并进一步支持我们之前从离体组织得出的研究结论。腺苷介导的心输出量和每搏量降低可能由A2B和/或A3 AR介导；然而，A1和A2 AR在整体心脏功能中也发挥作用。这些数据进一步为研究疾病状态下腺苷的心血管效应提供了强大的转化工具。
