权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of Nitric oxide synthase andCytochrome P450 enzyme on the inhibitory effect of sevoflumae on vascular relaxation

一氧化氮合酶和细胞色素P450酶对七氟哌啶醇抑制血管舒张作用的影响

基本信息

批准号：
14571463
负责人：
MIZUMOTO Kazuhiro
金额：
$ 2.11万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571463/
关键词：
Sevoflurane Nitric Oxide Cytochrome P450 シトクロームP450

项目摘要

<Isometric Force tension Recordings>After obtaining the various results as control, we checked both the Ach-induced relaxation of the rings pretreated with chlorzoxasone, a specific substrate of CYP450-2E1 and that of the rings from the rats to which CYP450-2E1 was induced by feeding with the water containing ethanol. From these results, the interaction between sevoflurane and CYP450-2E1 is suggested to be included in the mechanism underlying sevoflurane-induced inhibition of endothelium dependent vascular relaxation.<The measurement of nitric oxide synthase activity by Radioimmunoassay>The activity of nitric oxide synthase was tested with the method of measuring the conversion of radiolabelled L-arginine to L-citrulline. Sevoflurane did not affect the conversion L-arginine to L-citrulline which suggests that sevoflurane has no effect on nitric oxide synthase activity.<The confirmation of CYP450-2E1 induction with RT-PCR>The rings from the rats treatment with ethanol drinking were assured to overexpress CYP450-2E1 mRNA with the method of competitive RT-PCR.<The nitric oxide assay with chemoluminescence>After loading DAF FM-DA, nitroc oxide sensitive luminescence into the cultured bovine aortic endothelial cells, we tested the effect of sevoflurane on the intensity induced by bradykinin with or without the treatment of CYP450-2E1 induction. Under the treatment of CYP450-2E1 induction, the sevoflurane-induced inhibition of intensity was abolished.From these findings, it is suggested that CYP450-2E1 is one of the mediators producing Ach-induced endotherium dependent vascular relaxation, and sevoflurane expresses the inhibitory effect on the relaxation th* interference to the activity of CYP450-2E1 inside endothelial cells.

<等长力张力记录>在获得作为对照的各种结果后，我们检查了用CYP450-2E1的特定底物氯佐沙松预处理的Ach诱导的环的松弛，以及来自通过喂食含有乙醇的水诱导CYP450-2E1的大鼠的环的松弛。由这些结果表明，七氟烷和CYP450-2E1之间的相互作用被包含在七氟烷诱导的内皮依赖性血管舒张抑制的机制中。<通过放射免疫测定法测量一氧化氮合酶活性>通过测量放射性标记的L-精氨酸的转化率的方法来测试一氧化氮合酶的活性。为L-瓜氨酸。七氟烷不影响L-精氨酸向L-瓜氨酸的转化，这表明七氟烷对一氧化氮合酶活性没有影响。<通过RT-PCR确认CYP450-2E1诱导>通过竞争性RT-PCR方法确保饮酒处理的大鼠的环过度表达CYP450-2E1 mRNA。< 化学发光>将一氧化氮敏感的DAF FM-DA负载到培养的牛主动脉内皮细胞中后，我们测试了七氟烷对经过或不经过CYP450-2E1诱导处理的缓激肽诱导的强度的影响。在CYP450-2E1诱导作用下，七氟醚诱导的强度抑制被消除。由此推测，CYP450-2E1是产生Ach诱导的内皮依赖性血管舒张的介质之一，七氟醚通过干扰内皮细胞内CYP450-2E1的活性而表现出对舒张的抑制作用。