Paraventricular Nucleus P2X7 Receptors Aggravate Acute Myocardial Infarction Injury via ROS-Induced Vasopressin-V1b Activation in Rats  

作　　者：Wenjing Cheng Yinggang Sun Qin Wu Kokwin Ooi Yi Feng Chunmei Xia Danian Zhu 

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [2]Department of Cardiovascular Diseases,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China [3]Department of Medical Technology,Jiangsu Vocational College of Medicine,Yancheng 224005,China [4]Department of Integrative Medicine and Neurobiology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China

出　　处：《Neuroscience Bulletin》2021年第5期641-656,共16页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (31271215, 81770423, 81973945, and 81673766);the Health Vocational and Technical Education Research Program of Jiangsu Province, China (J201506)。

摘　　要：The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.

关 键 词：PVN P2X7 receptor VASOPRESSIN Reactive oxygen species C-FOS Myocardial ischemia 

分 类 号：R542.22[医药卫生—心血管疾病]