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（申请人提供）：心脏功能的控制主要通过自主神经系统的副交感神经和交感神经分支之间的平衡来实现。当这种平衡被改变时，心脏的控制可能会发生深刻且危及生命的改变。可能影响这种平衡的一个潜在因素是免疫系统响应炎症刺激而激活。免疫系统的局部激活最初是通过刺激组织内的肥大细胞发生的，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结果可能是组织内一氧化氮 (NO) 物质产生的变化。 NO 还被认为是心脏功能的重要调节剂。此外，炎症激活肥大细胞可能会通过增加细胞内合成酶一氧化氮合酶 (NOS) 的水平来增加组织产生 NO 的能力。这项研究的主要目标是确定 NO 如何影响心脏内有助于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 NOS 的水平。从豚鼠心脏分离出的组织含有所研究的神经元，将用于记录单个神经元的电反应，并确定一氧化氮对其活动的影响。为了研究肥大细胞刺激对 NOS 表达水平的影响，将组织暴露于肥大细胞刺激剂，然后使用显微镜进行分析以监测酶定位的变化。此外，还将在分子水平上分析组织，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，它将提供有关 NO 在心脏功能控制中的调节的重要信息。