NEUROPHARMACOLOGY OF THE BARORECEPTOR REFLEX

压力感受器反射的神经药理学

• 批准号: 3352265
• 负责人: FRANK J GORDON
• 金额: $ 14.84万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352265
• 关键词: afferent nerve; antihypertensive agents; baroreceptors; cardiovascular function; experimental brain lesion; gamma aminobutyrate; laboratory rat; medulla oblongata; neuroanatomy; neurogenic hypertension; neuropharmacology; neurotransmitters; pulmonary respiration; reflex; synapses

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.

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 参与中枢自主神经和心血管的受体 规定。 延髓中三个重要的综合“中心” 已确定在中枢心血管中起重要作用 控制。 它们是：1) 孤束核 (NTS)，2) 延髓尾侧腹外侧 (CVM)，以及 3) 头侧腹外侧 延髓（RVM）。 这些髓质区域似乎在神经网络内相连 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 这些区域之间以及神经递质和突触 受体负责它们之间的信息传递，以及其他 大脑区域尚未得到很好的表征。 拟议的研究将 提供生理学、药理学、生物化学和 用来解决这个问题的解剖学证据。 第一个 具体目标是评估 CVM 和 RVM 在中枢神经系统中的作用 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）确认 CVM 在中枢压力反射控制中的作用， 2) 确定CVM是否在中枢症状抑制过程中发挥作用 独立于压力感受器反射，3) 识别兴奋性氨基 RVN 中负责介导的酸性 (EAA) 受体类型 交感神经兴奋信息的神经传递，以及4)确定 中枢神经系统通路和突触受体是否介导 心血管反射可以与那些潜在的反射区分开来。 相同刺激引起的呼吸反射。 第二个具体目标 是在生化水平上检查氨基酸的功能 中枢心血管控制中的神经递质。 激活中枢 压力反射和交感兴奋通路与体内结合 RVM 和 CVM 的微透析将用于测量局部 EAA 和 GABA 释放与刺激同时发生。 此外，选择性破坏 传入心血管通路投射到这些髓质部位 结合组织微穿孔的体外神经化学分析 CVM 和 RVM 将用于进一步评估 EAA 和 GABA 的作用 延髓压力反射和心血管调节。 第三具体 目的将检查功能之间的解剖关系 确定了髓质中的“心血管”区域。 这些实验是 旨在提供结构基础以补充功能 从具体目标 1 和 2 下概述的研究中获得的结果。 了解中枢的组织和神经药理学 心血管控制可能有助于为设计提供合理的基础 可用于治疗病理异常的药物，例如 高血压。