NEUROPHARMACOLOGY OF THE BARORECEPTOR REFLEX

本研究的主要目的是识别和 神经通路、神经递质和突触的表征 受体参与中枢自主神经和心血管 调控 延髓的三个重要整合“中心” 在中枢性心血管疾病中起主要作用 控制 它们是：1）孤束核（NTS）， 尾侧延髓腹外侧区（CVM）; 3）头侧腹外侧区 髓质（RVM）。 这些髓质区域似乎在一个神经系统中 调节周围交感神经活动的网络 系统 然而，精确的功能和解剖关系 以及神经递质和突触 负责它们之间信息传递的受体，以及 大脑区域尚未得到很好的表征。 拟议的研究将 提供了生理学、药理学、生物化学和 解剖学证据来解决这个问题。 第一 具体目标将是评价中央兽医委员会和区域兽医委员会在中央 压力反射、心血管和呼吸调节。 这些实验 将采用电解损伤和显微注射药物， 延髓：1）证实了CVM在中枢压力反射控制中的作用， 2)确定CVM是否在中央symptoinhibitory过程中发挥作用 独立于压力感受器反射，3）识别兴奋性氨基 RVN中负责介导的EAA受体类型 交感神经兴奋信息的神经传递，以及4）确定 是否中枢神经系统通路和突触受体， 心血管反射可以与那些 由相同的刺激引起的呼吸反射。 第二个具体目标 是在生物化学水平上研究氨基酸的功能 中枢心血管控制中的神经递质。 激活中枢 压力感受性反射和交感神经兴奋通路结合体内 RVM和CVM的微透析将用于测量局部EAA和GABA 与刺激同时释放。 此外，选择性销毁 投射到这些髓质部位的传入心血管通路 结合体外神经化学分析的组织微穿孔， 将采用CVM和RVM进一步评估EAA和GABA的作用 延髓压力感受性反射和心血管调节。 第三特定 目的是检查功能性之间的解剖关系 确定了髓质中的“心血管”区域。 这些实验 旨在提供结构基础， 具体目标1和2项下概述的研究获得的结果。 了解中枢神经系统的组织和神经药理学 心血管控制可为设计提供合理依据 用于治疗病理异常的药物， 高血压

The principal aim of this research is the identification and characterization of neural pathways, neurotransmitters and synaptic receptors which participate in central autonomic and cardiovascular regulation. Three important integrative "centers" in the medulla oblongata have been identified which play a major role in central cardiovascular control. These are: 1) the nucleus of the tractus solitarius (NTS), 2) the caudal ventrolateral medulla (CVM), and 3) the rostral ventrolateral medulla (RVM). These medullary regions appear to be linked within a neural network that regulates the activity of the peripheral sympathetic nervous system. However, the precise functional and anatomical relationship between these areas, as well as the neurotransmitters and synaptic receptors responsible for information transmission between them, and other brain regions have not been well characterized. The proposed research will provide convergent lines of physiological, pharmacological, biochemical and anatomical evidence with which to address this question. The first Specific Aim will be to evaluate the role of the CVM and RVM in central baroreflex, cardiovascular and respiratory regulation. These experiments will employ electrolytic lesions and microinjection of drugs int the medulla to: 1) confirm the role of the CVM in central baroreflex control, 2) determine if the CVM plays a role in central sympthoinhibitory processes independently of baroreceptor reflexes, 3) identify the excitatory amino acid (EAA) receptor types in the RVN which are responsible for mediating neural transmission of sympathoexcitatory information, and 4) determine whether the CNS pathways and synaptic receptors which mediate cardiovascular reflexes can be distinguished from those which underlie respiratory reflexes evoked by identical stimuli. The second Specific Aim is to examine at the biochemical level the function of amino acid neurotransmitters in central cardiovascular control. Activation of central baroreflex and sympathoexcitatory pathways combined with in vivo microdialysis of the RVM and CVM will be used to measure local EAA and GABA release coincident with stimulation. In addition, selective destruction of afferent cardiovascular pathways projecting to these medullary sites combined with in vitro neurochemical analyses of tissue micropunches of the CVM and RVM will be employed to further assess the role of EAA's and GABA in medullary baroreflex and cardiovascular regulation. The third Specific Aim will examine the anatomical relationship between functionally identified "cardiovascular" regions in the medulla. These experiments are designed to provide the structural foundation to complement the functional results obtained from the studies outlined under Specific Aims 1 and 2. Knowledge of the organization and neuropharmacology of central cardiovascular control may help to provide a rational basis for the design of drugs useful for treating pathological abnormalities such as hypertension.