Protective Effect of Propofol on Endothelial Damage Induced by Reactive Oxygen Species in Rabbit

Kim, Kyung Hun; Suh, Jung Kook; Kim, Hwa Nyon; Cho, Sang Yoon

Abstract

BACKGROUND: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the isolated rabbit thoracic aorta. The aim of this study was to explore the influence of the propofol and midazolam against ROS in the isolated rabbit thoracic aortic endothelium.
METHODS
Eighteen white male rabbits (weighing 2.0-2.5 kg) were used. The thoracic aorta was dissected free and cut into rings (3-4 mm) and then suspended in a organ bath filled with 10 ml Krebs solution bubbled with 5% CO2 95% O2 at 37 degrees C. Aortic rings were then equilibrated for 90 min, and a resting tension of 1.5 g was applied. The Krebs solution was changed every 15 min. Isometric tension was recorded with transducer coupled to a data acqusition system (Biopac Inc. USA) on a PC. After precontraction with norepinephrine (NE, 10(-6)M), changes in tension were measured following the cumulative administration of acetylcholine (ACh 3x10(-7), 10(-6) and 3x10(-6)M) and nitroglycerin (NTG, 10(-5)M). Data are expressed as percentage of the 10 5 M NTG-induced relaxation (ACh/NTG). The ACh/NTG, before and after electrolysis were defined as the control and the experimental groups. The aortic rings were pretreated with propofol (3x10(-5), 10(-4), 3x10(-4) and 5.7x10(-4) M, n = 8, 10, 15, 13), midazolam (10(-4)M, n = 7), catalase (1,000 U/ml, n = 12), mannitol (3x10(-4)M, n = 5) or not pretreated group (Free, n = 6). After 30 minutes, the aortic rings were exposed to ROS generated by electrolysis (DC 9 V, 20 mA, aortic rings 1 cm away from electrode) in Krebs solution for 2 minutes, which was then changed for physiologic buffered salt solution. The aortic rings were precontracted with NE and vasorelaxation was induced with ACh and NTG at the above mentioned concentrations.
RESULTS
Propofol produced vasorelaxation of NE-precontracted thoracic aorta in a dose-dependent fashion in all groups of propofol (3x10(-5), 10(-4), 3x10(-4) and 5.7x10(-4)M) even after ROS attack (P < 0.05 vs control value). Catalase produced vasorelaxation after ROS attack (P < 0.05 vs control value).On the other hand, ACh-induced significant endothelium-dependent vasorelaxation were not observed in the midazolam or mannitol pretreated group or the non-pretreated group (P <0.05 vs control group).
CONCLUSIONS
These findings suggest that propofol and catalase preserve ACh induced endothelium-dependent vasorelaxation and that propofol has a concentration dependent ROS scavenging effect like catalase.