Sympathetic Neural Control Mechanisms in Hypertension

高血压的交感神经控制机制

基本信息

批准号：
7263185
负责人：
GREG M SWAIN
金额：
$ 13.51万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2009-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The proposed research (continuation of GM65958-01) seeks (i) to continue development of the diamond microelectrode for in vitro chronoamperometric measurements of neurotransmitter release and for use in microcapillary separation techniques coupled with electrochemical detection for the analysis of catecholamine neurotransmitters and metabolites in biological fluids, and (ii) to apply these tools to the study of sympathetic neural control mechanisms of arteries and veins in hypertension. Hypertension is a major health problem in the U.S. Those suffering from chronic high blood pressure are at high risk for organ damage and cardiovascular disease. Although the risk factors are known and treatments have been developed to alleviate symptoms, little is known about the underlying biological pathways and mechanisms. A goal of our research program is to gain a better understanding of how the sympathetic nervous system influences the development and maintenance of hypertension, and what effect chronic hypertension has on the cardiovascular system function and resistance to disease. Specific aims for the research include the following. Specific Aim 1: There are differences between sympathetic neural control of arteries and veins. These differences include the neurotransmitters released, receptors and mechanisms controlling release, and termination of the actions of the neurotransmitters. We seek to understand how these processes are altered in hypertension. Specific Aim 2: Endothelin-1 (ET-1) activity is increased in DOCA-salt hypertensive rats. It is also known that sympathetic activity is elevated in these animals and that ET-1 may be involved in changing sympathetic function in hypertension. We seek to understand the mechanism of ET-1 activity and how it can modulate NE release from sympathetic nerves. We also seek to understand if ET-1 can modulate ATP release from sympathetic nerves supplying mesenteric arteries and if this response is altered in hypertension.

描述（由申请人提供）：拟议的研究（GM65958-01的延续）寻求（i）继续开发钻石微电极，以进行体外的年度调节仪测量神经递质的释放，并用于与微毛细管分离技术一起用于分析，用于分析。在生物液中的儿茶酚胺神经递质和代谢产物，以及（ii）将这些工具应用于高血压中动脉和静脉的交感神经控制机制的研究。高血压是美国的主要健康问题，患有慢性高血压的人对器官损伤和心血管疾病的风险很高。尽管已知危险因素并已开发出治疗以减轻症状，但对潜在的生物途径和机制知之甚少。我们的研究计划的一个目标是更好地了解交感神经系统如何影响高血压的发展和维持，以及慢性高血压对心血管系统功能和对疾病的抵抗力的影响。研究的具体目标包括以下内容。特定目的1：动脉和静脉的交感神经控制之间存在差异。这些差异包括释放的神经递质，控制释放的受体和机制，以及终止神经递质的作用。我们试图了解这些过程如何在高血压中改变。特定目标2：内皮素-1（ET-1）活性在DOCA盐高血压大鼠中增加。众所周知，在这些动物中，交感神经活动升高，ET-1可能参与了高血压中的交感神经功能。我们试图了解ET-1活性的机制以及它如何调节彼达神经中的NE释放。我们还试图了解ET-1是否可以从提供肠系膜动脉的交感神经中调节ATP释放，以及在高血压中是否改变了这种反应。