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Role of Rho-kinase within the brain in abnormality of regulation of sympathetic nervous system in hypertension

脑内Rho激酶在高血压交感神经系统调节异常中的作用

基本信息

批准号：
13670721
负责人：
HIROOKA Yoshitaka
金额：
$ 2.3万
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：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670721/
关键词：
Rho Rho-kinase brain blood pressure sympathetic nervous system gene transfer signal transmission hypertension 遺伝子導入シグナル伝達

项目摘要

Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system, and has been shown to be involved in the maintenance of dendritic spines, in the process of axon outgrowth, and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is totally unknown. The blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY and SHR in the conscious state. The magnitude of decreases in these variables was also greater in SHR than in WKY. Furthermore, expression of RhoA in membrane and the activity of Rho-kinase in the NTS were enhanced in SHR as compared to WKY. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo, and that activation of this pathway may be involved in the central mechanisms of hypertension.

最近的研究表明，Rho/Rho-Kinase通路在多种细胞功能中发挥着重要作用，包括肌动蛋白的细胞骨架组织和血管平滑肌收缩。这一通路也存在于中枢神经系统中，并已被证明参与树突棘的维持、轴突生长过程和神经递质释放的调节。然而，它在中枢血压调节中的作用是完全未知的。在Wistar-京都大鼠(WKY)和自发性高血压大鼠(SHR)脑干孤束核(NTS)内微量注射Rho/Rho-Kinase通路后，血压、心率和肾交感神经活动均降低。然而，SHR组这些变量的下降幅度大于WKY组。此外，在清醒状态下，携带显性阴性Rho-Kinase的腺病毒载体可降低WKY和SHR的血压、心率和尿去甲肾上腺素排泄量。SHR组这些变量的下降幅度也大于WKY组。此外，与WKY相比，SHR膜上RhoA的表达和NTS中的Rho-Kinase活性均增强。这些观察表明，NTS中的Rho/Rho-Kinase通路在体内通过交感神经系统参与血压调节，该通路的激活可能参与高血压的中枢机制。