Role of Serotonin in Sympathetic Function

在失血量达到临界后，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、深度心动过缓和危及生命的低血压。中枢神经系统介导这种交感神经溶解反应的机制尚不清楚。对这种机制的更全面的了解可能会导致循环休克和其他交感神经反射异常激活的疾病的新治疗方法，如心脏后壁心肌梗死、主动脉狭窄相关的运动性晕厥或神经源性晕厥。在

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.