Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats

• Published in: Oxidative medicine and cellular longevity Vol. 2017; no. 2017; pp. 1 - 18
• Main Authors: Yuan, Hong-Bin, Yang, Feng, Fu, Hai-Long, Xu, Wen-Yun, Wang, Shuang-Ran, Zhang, Hao, Wang, Hao-Wei, Lu, Yan, Sun, Hai-Jing, Yao, Xue-Ya
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2017; Hindawi; Hindawi Limited
• Subjects: Anesthesiology; Animals; Apoptosis - drug effects; Arachidonic Acids - pharmacology; Benzamides - pharmacology; Carbamates - pharmacology; Cardiology; Cardiomyocytes; Cells, Cultured; Coronary vessels; Endocannabinoids - analysis; Endocannabinoids - metabolism; Fibroblasts; Handbooks; Hospitals; Hypoxia; Indoles - pharmacology; Ischemia; Kinases; Laboratory animals; Male; Malondialdehyde - blood; Malondialdehyde - metabolism; Myocardial Reperfusion Injury - chemically induced; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Ostomy; Pentobarbital - toxicity; Peroxidase - blood; Peroxidase - metabolism; Pharmacology; Propofol - pharmacology; Propofol - therapeutic use; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; Rodents; Signal Transduction - drug effects; Superoxide Dismutase - blood; Superoxide Dismutase - metabolism; Veins & arteries; China
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2017/2186383

Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS), malonaldehyde (MDA), and MPO (myeloperoxidase) and increased superoxide dismutase (SOD) production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.