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.
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