Sympathetic Neural Control Mechanisms in Hypertension

描述（由申请人提供）：提议的研究（GM65958-01的延续）寻求(i)继续开发金刚石微电极，用于体外定时电流测量神经递质释放，并用于微毛细管分离技术与电化学检测相结合，用于分析生物液体中的儿茶酚胺神经递质和代谢物，以及（ii）将这些工具应用于研究高血压动脉和静脉的交感神经控制机制。高血压是美国的一个主要健康问题。患有慢性高血压的人患器官损伤和心血管疾病的风险很高。虽然已知危险因素，并且已经开发出缓解症状的治疗方法，但对潜在的生物学途径和机制知之甚少。我们的研究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疾病抵抗力的影响。本研究的具体目的包括：具体目的1：交感神经对动脉和静脉的控制存在差异。这些差异包括神经递质释放、受体和控制释放的机制，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。特异性目的2:doca盐高血压大鼠内皮素-1 （ET-1）活性升高。我们也知道，这些动物的交感神经活动升高，ET-1可能参与改变高血压患者的交感神经功能。我们试图了解ET-1活动的机制，以及它如何调节交感神经的NE释放。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发生改变。

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.