PROTECTIVE EFFECT OF PROPOFOL ON FREE RADICAL INDUCED IMPAIRMENT OF VASCULAR SMOOTH MUSCLE REACTIVITY.

异丙酚（2,6-二异丙酚）已被证明可以减轻氧化应激诱导的组织损伤。然而，关于异丙酚对活性氧诱导的血管反应性损伤的影响，我们知之甚少。因此，本研究旨在研究异丙酚对活性氧诱导的α-肾上腺素能受体介导的血管收缩和离体血管内皮依赖性松弛反应的影响。将雄性白化兔肠系膜动脉环制品悬浮于含有改良克雷布-林格溶液的10 ml器官液中，测量其等长力的变化。研究了Fenton试剂（150 μM H_2O_2 + 100 μM FeSO_4）、过氧化氢（H_2O_2; 150 μM）和FeSO_4 （100 μM）生成的羟基自由基（HO）对去甲肾上腺素（NE; 1μM）诱导的收缩和乙酰胆碱（ACh; 1μM）诱导的松弛的影响，以及异丙酚的保护作用。此外，还采用鲁米诺增强化学发光法和电子自旋共振（ESR）光谱法对异丙酚的自由基清除性能进行了评价。事先暴露于HO和H_2O_2的环状材料对ne诱导的张力发展的抑制作用分别为对照值的47.0±8.05%和40.2±2.78%。将环形制备物单独暴露于FeSO4中没有影响。10μM浓度的异丙酚对ne诱导的收缩反应有增强作用，但对Fenton试剂和H_2O_2对ne诱导的收缩反应的抑制作用分别为97.4±3.54和90.4±4.20。环制剂与含Fenton试剂和H_2O_2的Krebs-Ringer溶液孵育后，ach诱导的松弛作用分别为对照组的79.8±2.63%和73.0±2.77%。环制物单独暴露于FeSO_4中没有效果。异丙酚（10 μM，其本身对乙酰胆碱诱导的舒张无影响）可抑制HO或H_2O_2对乙酰胆碱诱导的内皮依赖性舒张的抑制作用。异丙酚对Fenton试剂和h_2o_2诱导的鲁米诺化学发光增强均呈剂量依赖性减弱。ESR谱分析提供了异丙酚和地普利麻【〇！R】分别在1 μM和10 μM浓度下抑制DMPO-HO自旋加合物的形成，并呈剂量依赖性。本研究结果表明，临床上适当浓度的异丙酚对活性氧引起的离体兔肠系膜动脉血管反应性损伤具有保护作用，可能与异丙酚对过氧化氢的清除能力有关。少

Propofol (2,6-diisopropylohenol) has been shown to attenuate oxidative stress-induced tissue injury. However, little is known concerning the effects of propofol on the reactive oxygen species-induced impairment of vascular reactivity. Therefore, this study was designed to examine the effect of propofol on reactive oxygen species-induced modification of the α-adrenoceptor mediated vascular contraction and in endothelium-dependent relaxation responses of the isolated blood vessels. The ring preparations of mesenteric artery from male albino rabbits were suspended in 10 ml organ baths containing modified Krebs-Ringer solution and changes in isometric force were measured. Effects of prior exposure the ring preparations to hydroxyl radical (HO) generated from Fenton's reagent (150 μM H_2O_2 plus 100 μM FeSO_4), hydrogen peroxide (H_2O_2 ; 150 μM) and FeSO_4 (100 μM ) on norepinephrine (NE ; 1μM)-induced contraction and acetylcholine (ACh ; 1 μM)-induced relaxation and protective effects of … More propofol were investigated. In addition, free radical scavenging property of propofol was also assessed using luminol-enhanced chemiluminescence method and electron spin resonance (ESR) spectroscopy. Prior exposure of ring preparations to HO and H_2O_2 inhibited NE-induced tension development to 47.0 ± 8.05 % and 40.2 ± 2.78 % of control values, respectively. Exposure the ring preparation to FeSO4 alone was without effect. While propofol, concentration of 10μM potentiated the NE-induced contraction by itself, it protected against the observed inhibitory effect on NE-induced contractile responses by Fenton's reagent and H_2O_2 to 97.4 ± 3.54 and 90.4 ± 4.20, respectively. Incubation of ring preparations with Krebs-Ringer solution containing Fenton's reagent and H_2O_2 inhibited ACh-induced relaxation to 79.8 ± 2.63 % and 73.0±2.77% of control values, respectively. Exposure the ring preparation to FeSO_4 alone was without effect. Propofol (10 μM, which has no effect on ACh-induced relaxation by itself) protected against the observed inhibitory effect on ACh-induced endothelium-dependent relaxation by HO or H_2O_2. Both Fenton's reagent- and H_2O_2-induced enhancements of luminol-chemilumionescence were attenuated by addition of propofol in a dose-dependent manner. Analysis of ESR spectroscopy provided the evidence that propofol and Diprivan【○!R】 in concentration of 1 and 10 μM, respectively, inhibited the formation of DMPO-HO spin adducts in a dose-dependently. Results obtained in present study demonstrated that clinically relevant concentration of propofol could protect against the impairment of vascular reactivity of isolated rabbit mesenteric artery induced by reactive oxygen species probably due to its scavenging ability of hydrogen peroxide. Less