Role of Serotonin in Sympathetic Function

在失血达到临界量后，通常有助于维持血压的代偿性神经反应突然失效，导致血管舒张、严重心动过缓和危及生命的低血压。介导这种交感神经阻滞反应的中枢神经系统机制尚不清楚。对这些机制的更全面的理解可能会导致循环休克和其他具有交感神经反射异常激活的疾病的新治疗，如心脏后下壁的心肌梗死，与主动脉瓣狭窄相关的劳力性晕厥或神经源性晕厥。在 由于麻醉对自主神经功能的影响，设计用于检查这些反应的体内模型受到限制。这个建议的目的是阐明的作用，后脑β-肾上腺素能细胞和受体介导的机制，在突然失去交感神经活动，伴随着严重的失血在清醒的大鼠。具体而言，研究旨在确定出血期间血清素的来源和介导交感神经退缩的受体群体。拟议的实验涉及 经典生理学模型的新用途，以研究离散的后脑神经元和受体群体在未麻醉大鼠交感神经功能调节中的作用。将联合收割机神经束示踪与神经元表型和功能的免疫组织化学标记物相结合的解剖学研究将用于确定参与交感神经反射的5-羟色胺的来源和投射部位。本提案中概述的新技术将有助于确定后脑多巴胺能细胞和受体对交感神经调节的功能，特别是对出血反应的功能，这一目标迄今为止一直受到麻醉对出血反应和多巴胺能神经调节的混淆影响的阻碍。 功能

Following a critical amount of blood loss, compensatory neural responses that normally help maintain blood pressure suddenly fail, causing vasodilation, profound bradycardia and life-threatening hypotension. The central nervous system mechanisms that mediate this sympatholytic response are unknown. A more comprehensive understanding of such mechanisms could lead to novel treatments for circulatory shock and other disorders with aberrant activation of sympatholytic reflexes such as myocardial infarct of the inferoposterior wall of the heart, exertional syncope associated with aortic stenosis or neurogenic syncope. In vivo models devised to examine these responses have been limited due to the effects of anesthesia on autonomic function. The objective of this proposal is to elucidate the role of hindbrain serotonergic cellular- and receptor mediated mechanisms in the sudden loss of sympathetic activity that accompanies severe blood loss in the conscious rat. Specifically, studies have been designed to identify the source of serotonin and the receptor populations that mediate sympathetic withdrawal during hemorrhage. The proposed experiments involve novel uses of classic physiological models to study the role of discrete hindbrain neuronal and receptor populations in the regulation of sympathetic function in unanesthetized rats. Anatomical studies that combine neuronal tract tracing with immunhistochemical markers of neuronal phenotype and function will be used to determine the source and projection site of serotonin involved in sympathetic reflexes. The novel techniques outlined in this proposal will help to determine hindbrain serotonergic cellular and receptor function on sympathetic regulation in general and on hemorrhage responses in particular, a goal which has, until now, been hampered by the confounding influence of anesthesia on hemorrhage responses and serotonergic function.