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，导致血管扩张、严重的心动过缓和危及生命的低血压。介导这种交感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了解可以为循环休克和其他交感神经反射异常激活的疾病带来新的治疗方法，如心脏后下壁心肌梗死、伴主动脉狭窄的劳力性晕厥或神经源性晕厥。在……里面 由于麻醉对自主神经功能的影响，为检查这些反应而设计的活体模型一直受到限制。这项建议的目的是阐明后脑5-羟色胺能细胞和受体介导的机制在伴随严重失血的清醒大鼠交感神经活动突然丧失中的作用。具体地说，研究旨在确定5-羟色胺的来源和在出血过程中介导交感神经退出的受体群体。拟议的实验包括 经典生理学模型的新应用来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。解剖学研究将神经束追踪与神经元表型和功能的免疫组织化学标记相结合，以确定参与交感反射的5-羟色胺的来源和投射部位。这项提案中概述的新技术将有助于确定后脑5-羟色胺能细胞和受体在交感神经调节上的功能，特别是在出血反应上，这一目标到目前为止一直受到麻醉对出血反应和5-羟色胺能的混淆影响的阻碍。 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.