Regulation and actions of NO in the cardiac plexus

描述（由申请人提供）：心脏功能的控制主要通过自主神经系统副交感神经和交感神经的平衡来实现。当这种平衡被改变时，对心脏的控制可能会发生深刻的、威胁生命的变化。一个可能影响这种平衡的潜在因素是免疫系统对炎症刺激的反应。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。肥大细胞活化的一个后果可能是组织内一氧化氮（NO）物质产生的变化。一氧化氮也被认为是心功能的重要调节因子。此外，肥大细胞的炎症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一氧化氮的能力。本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功能的神经元的功能，并检查心脏肥大细胞的激活是否可以改变心脏内一氧化氮的水平。从豚鼠心脏中分离出来的组织，包含正在研究的神经元，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NOS表达水平的影响，将组织暴露于肥大细胞刺激剂中，然后用显微镜分析，监测酶定位的变化。此外，组织将在分子水平上进行分析，以寻找酶表达和mRNA水平的变化。本研究结果将为免疫系统和神经系统在心脏功能控制中的相互作用提供新的信息。特别是，它将提供关于NO在心脏功能控制中的调节和重要信息。

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.