Antioxidant effects and mechanism of thiopental and propofol on the rabbit abdominal aortic endothelial dependent vasorelaxation against reactive oxygen species

provided the original work is properly cited. CC Reactive oxygen species (ROS), which are also generated in a normal condition in certain quantities, are generated in large quantities by ischemia or by oxygen resupply at the time of reperfusion and not reduced by the normal antioxidant systems of the body, eventually causing reperfusion injury in tissues [1]. In this study, we investigated whether thiopental and propofol, which are intravenous anesthetics, decrease endothelium injury by ROS and evaluated the mechanism for the decrease by causing endothelium-dependent relaxation of rabbit abdominal aortas. All the experiments in this study were done after obtaining the approval of the Institutional Animal Care and Use Committee. Twenty four male New Zealand white rabbits (KOATECH, Pyeongtaek, Korea) weighing 2.0-2.5 kg were anesthetized with 3-5 vol% sevoflurane and 100% oxygen 4 L/min. Heparin 600 IU/kg was intravenously injected through the auricular marginal vein. Ten minutes after the heparin injection, the rabbit carotid artery was sectioned for exsanguinations, and the infra renal abdominal aorta was obtained. ROS was generated by performing electrolysis (EL) of a K-H solution in an experimental bath. Two circular Platinum wire electrodes (7 mm) were positioned at the lower part of the experimental bath. Hemangioendothelial injury by ROS was induced by exposure to 15 mA DC constant current for 35 seconds (EL+) [2,3]. Thiopental and propofol, intravenous anesthetics, were put into the experimental bath at concentrations of 10 M, 3 × 10 M, 10 M, and 3 × 10 M and at concentrations of 10 M, 3 × 10 M, 10 M, and 3 × 10 M, respectively. After 15 minutes of pretreatment, EL+ was performed for 35 seconds. The used K-H solution was replaced with new K-H solution. After contracting the abdominal aorta by putting in NE, ACh at concentrations of 3 × 10 M, 10 M, 3 × 10 M, and 10 M was continuously added to the bath to relax the annular slices. Cu/Zn superoxide dismutase (SOD) and catalase, which are important antioxidative enzymes, were pretreated with 0.8 mM diethyldithiocarbamate (DETCA) [4], a SOD inhibitor, for 30 minutes and with 50 mM 3-amino-1,2,4-triazole (3AT) [5], a catalase inhibitor, for 60 minutes. While pretreating with DETCA and 3AT for 30 and 60 minutes in the experimental bath, respectively, thiopental (3 × 10 M) or propofol (3 × 10 M) was, respectively, added to the experimental bath 15 minutes before the completion of the pretreatment. After 15 minutes, EL was performed to generate ROS, and then the K-H solution was replaced with a new K-H solution. The annular slices were contracted and relaxed by adding NE and Ach to the bath. All the data were expressed as the “Mean ± Standard Error” and the degree of ACh relaxation, calculated in percentage, was used as the control value. The comparison of the results between the pretreated groups with respect to the thiopental and propofol concentrations was done by a one-way ANOVA and Dunnett test was done for a post-hoc test. An unpaired t-test was done to compare the aortic