Sympathetic Neural Control Mechanisms in Hypertension

高血压的交感神经控制机制

• 批准号: 6967340
• 负责人: GREG M SWAIN
• 金额: $ 19.37万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967340
• 关键词: adenosine triphosphate; angiotensin /renin /aldosterone hypertension; biomedical equipment development; capillary electrophoresis; dietary sodium; electrical conductance; electrophysiology; endothelin; genetic strain; laboratory rat; membrane transport proteins; mesenteric artery; microelectrodes; neurophysiology; neurotransmitter transport; norepinephrine; sympathetic nervous system; vascular smooth muscle nervous control; veins

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（申请人提供）：拟议研究（GM 65958 -01的继续）寻求（i）继续开发金刚石微电极，用于神经递质释放的体外计时电流测量和用于与电化学检测结合的微毛细管分离技术，用于分析生物流体中的儿茶酚胺神经递质和代谢物，并将这些工具应用于高血压动脉和静脉交感神经控制机制的研究。高血压在美国是一个主要的健康问题。那些患有慢性高血压的人有很高的器官损伤和心血管疾病的风险。虽然已知的风险因素和治疗方法已经开发出来，以减轻症状，但对潜在的生物学途径和机制知之甚少。我们研究计划的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抵抗疾病的影响。研究的具体目标如下。具体目的1：交感神经对动脉和静脉的控制存在差异。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神经递质作用的终止。我们试图了解这些过程在高血压中是如何改变的。具体目标2：DOCA盐高血压大鼠内皮素-1（ET-1）活性升高。还已知交感神经活性在这些动物中升高，并且ET-1可能参与改变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交感神经释放NE。我们还试图了解ET-1是否可以调节供应肠系膜动脉的交感神经的ATP释放，以及这种反应是否在高血压中改变。