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Regulation and actions of NO in the cardiac plexus

NO 在心丛中的调节和作用

基本信息

批准号：
6953298
负责人：
JEAN C HARDWICK
金额：
$ 20.97万
依托单位：
ITHACA COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-08-01 至 2009-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The control of cardiac function is achieved primarily through a balance between the parasympathetic and sympathetic branches of the autonomic nervous system. When this balance is altered, there can be profound and life threatening alterations in the control of the heart. One potential factor that may impact this balance is the activation of the immune system in response to inflammatory stimuli. Localized activation of the immune system initially occurs via the stimulation of mast cells located within the tissue, which release potent bioactive mediators. One consequence of this mast cell activation may be a change in the production of the substance nitric oxide (NO) within the tissue. NO is also known to be an important regulator of cardiac function. In addition, activation of mast cells with inflammation may increase the ability of tissues to produce NO by increasing the levels of the synthetic enzyme, nitric oxide synthase (NOS) in cells. The major goal of this study is to determine how NO affects the function of neurons within the heart that help control cardiac function and to examine whether activation of mast cells in the heart can alter the levels of NOS in the heart. Isolated tissue from guinea pig hearts, containing the neurons under study, will be used to record the electrical responses from individual neurons and determine the effects of NO on their activity. To study the effect of mast cell stimulation on NOS expression levels, tissues will be exposed to mast cell stimulators and then analyzed using microscopy to monitor changes in enzyme localization. In addition, the tissue will be analyzed at the molecular level to look for changes in enzyme expression and mRNA levels. The results of this study will provide new information on the interaction between the immune system and the nervous system in the control of cardiac function. In particular, it will provide important information concerning the regulation and of NO in the control of cardiac function.

描述(由申请人提供)：心脏功能的控制主要是通过自主神经系统的副交感和交感分支之间的平衡实现的。当这种平衡被改变时，心脏的控制可能会发生深刻的、危及生命的变化。可能影响这种平衡的一个潜在因素是免疫系统对炎症刺激的反应被激活。免疫系统的局部激活最初是通过刺激位于组织内的肥大细胞来实现的，肥大细胞释放出有效的生物活性介质。肥大细胞激活的一个后果可能是改变组织内物质一氧化氮(NO)的产生。NO也被认为是心脏功能的重要调节因子。此外，炎症时肥大细胞的激活可能通过增加细胞中合成酶一氧化氮合酶(NOS)的水平来增加组织产生NO的能力。这项研究的主要目的是确定一氧化氮如何影响心脏内帮助控制心脏功能的神经元的功能，并检查心脏中肥大细胞的激活是否可以改变心脏中的一氧化氮合酶水平。从含有被研究神经元的豚鼠心脏中分离出的组织将被用来记录单个神经元的电反应，并确定NO对其活动的影响。为了研究肥大细胞刺激对一氧化氮合酶表达水平的影响，将组织暴露在肥大细胞刺激物中，然后使用显微镜分析酶定位的变化。此外，将在分子水平上对组织进行分析，以寻找酶表达和mRNA水平的变化。这项研究的结果将为免疫系统和神经系统在控制心脏功能方面的相互作用提供新的信息。特别是，它将为心脏功能的调节和NO的控制提供重要的信息。