Relationship between mitochondrial ATP sensitive potassium channels and reactive oxygen species in cardiovascular tissue.

线粒体 ATP 敏感钾通道与心血管组织中活性氧的关系。

基本信息

批准号：
15590230
负责人：
KIMURA Shoji
金额：
$ 2.37万
依托单位：
Kagawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

This study aimed to examine the involvement of mitochondria-derived reactive oxygen species (ROS) in the signaling pathway and the vasoconstrictor mechanism of Ang II. Using 5-hydroxydecanoate (5-HD ; a specific inhibitor of mitochondrial ATP-sensitive potassium channels (mitoKATP)) and tempol (a superoxide dismutase mimetic), the effects of Ang II and diazoxide (a mitoKATP opener), were compared on redox-sensitive mitogen-activated protein kinase (MAPK) activation in rat vascular smooth muscle cells (RVSMC) in vitro and in rat aorta in vivo. Stimulation of RVSMC by Ang II or diazoxide increased phosphorylated MAPK (ERK1/2,p38 and JNK) as well as superoxide production ; which were then suppressed by 5-HD pretreatment in a dose dependent manner, except for ERK1/2 activation by Ang II. The same events were reproduced in rat aorta in vivo. Ang II like diazoxide depolarized the mitochondrial membrane potential (ΔΨ_M) of RVSMC, which was inhibited by 5-HD. 5-HD did not modulate Ang II induc … More ed calcium mobilization in RVSMC and did not affect on the vasoconstrictor effect in either acute or chronic phases of Ang II induced hypertension. These results reveal that Ang II stimulates mitochondrial ROS production through the opening of mitoKATP in the vasculature, leading to reduction of ΔΨ_M and redox-sensitive activation of MAPK ; however, generated ROS from mitochondria do not contribute to Ang II-induced vasoconstriction. See Hypertension 2005;45(3):438-44 and Hypertension 2005 (in press) in detail. The related articles also demonstrated as shown below ;1)Acute administration of Ang II and phenylephrine to conscious rats provoked redox-sensitive activation of MAPK in the heart and aorta. (Hypertension. 2004;43:117-24, J Pharmacol Sci. 2004;96;406-10)2)The mechanisms of Ang II induced vasoconstriction may shift from being non-sensitive to ROS to sensitive within 12 hours. (J Hypertens. 2004;22:2161-8.)3)(β-adrenoceptor stimulation provokes cardiac oxidative stress, while the generated ROS are responsible for the activation of MAPK cascade. (Cardiovasc Res. 2005;65:230-8.) Less

这项研究旨在研究线粒体衍生的活性氧（ROS）在ANG II的信号传导途径和血管收缩机理中的参与。使用5-羟基二烷（5-HD；线粒体ATP敏感钾通道（Mitokatp））的特定抑制剂（Mitokatp））和tempool（超氧化物歧义酶模拟酶），Ang II和Diizoxide的影响（MitokaTP开瓶器）对补氧敏感的蛋白质蛋白蛋白蛋白蛋白蛋白蛋白蛋白蛋白蛋白蛋白含量（一种）体外和大鼠主动脉中的肌肉细胞（RVSMC）。 ANG II或二氮氧化物对RVSMC的刺激增加了磷酸化的MAPK（ERK1/2，P38和JNK）以及超氧化物的产生；然后以剂量依赖性的方式通过5-HD预处理抑制，除了ANG II激活ERK1/2。大鼠主动脉在体内复制了相同的事件。像二氮氧化物一样，ANG II部署了RVSMC的线粒体膜电位（Δψ_M），该电位被5-HD抑制。 5-HD没有调节ANG II引起的……RVSMC中更多的ED钙动员，也不会影响ANG II诱导的高血压的急性或慢性阶段的血管收缩效应。这些结果表明，ANG II通过在脉管系统中的MitokATP开放刺激线粒体ROS的产生，从而导致MAPK的Δψ_M和氧化还原敏感激活的减少。但是，线粒体产生的ROS并不促进ANG II诱导的血管收缩。参见Hypermension 2005; 45（3）：438-44和Hypertension 2005（印刷中）。相关文章也如下所示：1）ANG II和苯肾上腺素对意识大鼠的急性给药引起了心脏和主动脉中MAPK对氧化还原敏感的激活。（Hypermension。2004; 43：117-24，J PharmacolSci。2004; 96; 406-10）2）ANG II诱导的血管收缩的机理可能会在12小时内从非敏感性转移到ROS转移到敏感。（JHypertens。2004; 22：2161-8。）3）（β-肾上腺素受体刺激会引起心脏氧化应激，而产生的ROS负责MAPK CASCADE的激活。（CardiovascRes。2005; 65：230-8。）较少

项目成果

期刊论文数量（42）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rahinan M. et al.: "Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart."Eur.J.Pharmacol.. 485. 243-249 (2004)

Rahinan M. 等人：“血管紧张素 II 通过小鼠主动脉和心脏中的血管紧张素 AT1A 和 AT1B 受体刺激超氧化物的产生。”Eur.J.Pharmacol.. 485. 243-249 (2004)

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Effects of ATI receptor blockade on renal injury and mitogen-activated protein kinase activity in Dahl salt-sensitive rats.

ATI 受体阻断对 Dahl 盐敏感大鼠肾损伤和丝裂原激活蛋白激酶活性的影响。

DOI：
发表时间：
2004
期刊：
Kidney Int. 65
影响因子：
0
作者：
Zhang GX.et al.;Fujisawa Y.et al.;Nishiyama A.et al.;Nishiyama A.et al.;Rahman M.et al.;Nishiyama A.et al.
通讯作者：
Nishiyama A.et al.

Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart.