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

Role of reactive oxygen species within the vasomotor center of the brain in hypertension

大脑血管运动中枢活性氧在高血压中的作用

基本信息

批准号：
15590757
负责人：
HIROOKA Yoshitaka
金额：
$ 2.24万
依托单位：
KYUSHU 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

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590757/
关键词：
Reactive oxygen species blood pressure heart rate sympathetic nervous system gene brain nitric oxide norepinephrine 交感神経系酸化ストレス高血圧

项目摘要

Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species(ROS) are increased in the rostral ventrolateral medulla(RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats(SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP. We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats(WKY). Thiobarbituric acid-reactive substances were increased in SHRSP compared with WKY. ROS were also measured by electron spin resonance(ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase(SOD) activity in the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity. These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP. We also examined the role of inducible nitric oxide synthase(iNOS) in the RVLM in the control of blood pressure and sympathetic nerve activity. We fond that overexpression of iNOS in the RVLM increases blood pressure via activation of the sympathetic nervous system, which is mediated by an increase in oxidative stress.

高血压时氧化应激增加。本研究的目的是确定是否活性氧（ROS）增加的头端腹外侧延髓（RVLM）在脑干，血管中枢所在的，在易卒中的自发性高血压大鼠（SHRSP），如果是这样的话，以确定是否增加的ROS有助于高血压的神经机制在SHRSP。我们测量了SHRSP RVLM中的ROS水平，并与Wistar-Kyoto大鼠（WKY）进行了比较。SHRSP的硫代巴比妥酸反应物质较WKY增加。还通过电子自旋共振（ESR）光谱测量ROS。SHRSP RVLM的ESR信号衰减速率较WKY明显增加，这种增加可被羟自由基清除剂二甲基硫脲消除。增加的ESR信号衰减减少到相同程度的存在下，去铁胺，过氧化氢酶，和Tiron，表明羟基自由基是来自超氧阴离子和过氧化氢。此外，总超氧化物歧化酶（SOD）活性在RVLM降低血压SHRSP，但不WKY，和MnSOD过表达的SHRSP的RVLM降低血压和抑制交感神经活动。这些结果表明，超氧阴离子在RVLM，产生羟基自由基，增加在SHRSP的高血压的神经机制作出贡献。我们还研究了诱导型一氧化氮合酶（iNOS）在RVLM中控制血压和交感神经活动的作用。我们发现RVLM中iNOS的过度表达通过交感神经系统的激活而升高血压，这是由氧化应激的增加介导的。