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活性氧对大鼠主动脉的不同收缩作用:过氧化氢对ATP受体的选择性激活

Differential contractile actions of reactive oxygen species on rat aorta: selective activation of ATP receptor by H2O2.

作者信息

Shen J Z, Zheng X F, Kwan C Y

机构信息

Department of Pharmacology, Faculty of Medicine, Zhejiang University, Hangzhou, PR China.

出版信息

Life Sci. 2000 Apr 14;66(21):PL291-6. doi: 10.1016/s0024-3205(00)00539-7.

DOI:10.1016/s0024-3205(00)00539-7
PMID:10823352
Abstract

This study aims to examine the effects of different reactive oxygen species (ROS) on the resting tension of endothelium-denuded rat aortic rings. In these preparations, H2O2 (30 microM) induced a fast and transient contraction, which could be abolished by pretreatment of catalase (800 U/ml), but not affected by superoxide anion scavenger, superoxide dismutase (SOD; 150 U/ml) or the hydroxyl free radical scavenger, DMSO/mannitol (each 3 mM). In contrast, pyrogallol, a putative superoxide anion donor, induced a biphasic contraction, which could be abolished by SOD, but not by catalase or DMSO/mannitol. Unlike H2O2 and pyrogallol, Vitamin C(VitC)/Fe2+ (each 100 microM), a commonly used hydroxyl radical-generating system, triggered a tonic contraction which could be prevented by DMSO/mannitol, but not by SOD or catalase. Interestingly, H2O2-induced contraction could be concentration-dependently (10-100 microM) inhibited by suramin and reactive blue-2 (RB-2), two widely used ATP receptor antagonists. On the other hand, suramin or RB-2, at concentration up to 100 microM, affected neither pyrogallol nor VitC/Fe2+-induced contraction. In conclusion, we showed for the first time that different ROS could contract rat aorta with different mechanisms of action, and H2O2 elicits a transient contraction probably as a result of the ATP receptor activation.

摘要

本研究旨在探讨不同活性氧(ROS)对去内皮大鼠主动脉环静息张力的影响。在这些实验制剂中,过氧化氢(H2O2,30微摩尔)诱导快速且短暂的收缩,该收缩可被过氧化氢酶预处理(800单位/毫升)消除,但不受超氧阴离子清除剂超氧化物歧化酶(SOD,150单位/毫升)或羟自由基清除剂二甲基亚砜/甘露醇(各3毫摩尔)影响。相反,连苯三酚,一种假定的超氧阴离子供体,诱导双相收缩,该收缩可被SOD消除,但不能被过氧化氢酶或二甲基亚砜/甘露醇消除。与H2O2和连苯三酚不同,常用的羟自由基生成系统维生素C(VitC)/亚铁离子(各100微摩尔)引发强直性收缩,该收缩可被二甲基亚砜/甘露醇阻止,但不能被SOD或过氧化氢酶阻止。有趣的是,H2O2诱导的收缩可被两种广泛使用的ATP受体拮抗剂苏拉明和活性蓝-2(RB-2)浓度依赖性地(10 - 100微摩尔)抑制。另一方面,浓度高达100微摩尔的苏拉明或RB-2对连苯三酚或VitC/亚铁离子诱导的收缩均无影响。总之,我们首次表明不同的ROS可通过不同作用机制使大鼠主动脉收缩,且H2O2引发短暂收缩可能是ATP受体激活的结果。

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