CENTRAL CARDIOVASCULAR CONTROL: NORMAL AND HYPERTENSIVE

中央心血管控制：正常和高血压

• 批准号: 3449968
• 负责人: SHAUN F MORRISON
• 金额: $ 5.32万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3449968
• 关键词: antidromic impulse; baroreceptors; blood pressure; electrophysiology; gamma aminobutyrate; histochemistry /cytochemistry; hypertension; immunochemistry; neural information processing; neurotransmitters; nontherapeutic iontophoresis; reflex; solitary tract nucleus; sympathetic nervous system; synapses

Recent research on central cardiovascular control indicates the existence of a population of neurons in the lateral medullary reticular formation that provides a final common pathway conveying the excitatory drive to the spinal sympathetic nucleus that is critical for the maintenance of basal sympathetic tone. As described in the proposal, the characterization of these neurons will provide new information on the central neural mechanisms underlying the sympathetic control of blood pressure. The proposed studies will focus on the hypothesis that neurons in the rostral ventrolateral medulla (RVL) that contain the adrenaline-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT) mediate the tonic bulbospinal excitation of sympathetic preganglionic neurons (SPN) necessary for the support of resting blood pressure. Extracellular recording and antidromic activation techniques are combined with baroreceptor reflex activation and computer-aided analysis to identify sympathoexcitatory neurons in RVL that project to the sympathetic intermediolateral nucleus. Immunocytochemical staining is used to determine the proximity of the recording sites of these neurons to the locations of neurons containing PNMT (C1 cell group). Additional experiments are designed to examine (1) the baroreceptor reflex pathway providing an inhibitory control of the activity of these cells and (2) the activation of RVL sympathetic neurons from hypothalamic pressor sites. Microiontophoretic application of antagonist drugs will be used to classify the transmitter system(s) mediating the effects of RVL activation on the activity of SPNs. Together these data would not only increase our knowledge of the basic neural mechanisms involved in central blood pressure regulation, they might also provide a basis for (1) the evaluation of the role of altered neural function in hypertensive disease and (2) the design of pharmacologic approaches to antihypertensive therapy. The former possibility is tested in a final series of experiments to determine if the sympathetic hyperactivity of the spontaneously hypertensive rat is associated with increased activity of the sympathoexcitatory neurons in the C1 region of the RVL.

最近对中枢心血管控制的研究表明存在 外侧髓质网状结构中的神经元群 它提供了一条最终的共同途径，将兴奋性驱动力传递给 脊髓交感核对于维持基础神经功能至关重要 同情的语气。 正如提案中所描述的， 这些神经元将提供有关中枢神经机制的新信息 是交感神经控制血压的基础。 拟议的研究 将重点关注这样的假设：嘴侧腹外侧神经元 髓质（RVL）含有肾上腺素合成酶， 苯乙醇胺 N-甲基转移酶 (PNMT) 介导强直球脊髓 交感神经节前神经元 (SPN) 的兴奋是 支持静息血压。 细胞外记录和逆向性 激活技术与压力感受器反射激活相结合 计算机辅助分析识别 RVL 中的交感兴奋神经元 投射到交感中间外侧核。 免疫细胞化学 染色用于确定这些记录位点的接近程度 神经元到含有 PNMT 的神经元（C1 细胞组）的位置。 额外的实验旨在检查（1）压力感受器反射 途径提供对这些细胞的活性的抑制控制和 (2)下丘脑升压源激活RVL交感神经元 网站。 拮抗剂药物的微离子导入应用将用于 对介导 RVL 激活效应的递质系统进行分类 关于 SPN 的活动。 这些数据加在一起不仅会增加我们的 了解中枢血压的基本神经机制 监管，它们还可以为（1）评估提供基础 神经功能改变在高血压疾病中的作用以及（2）设计 抗高血压治疗的药理学方法。 前者 在最后一系列实验中测试可能性，以确定是否 自发性高血压大鼠的交感神经亢进是 与交感神经兴奋性神经元活动增加有关 RVL 的 C1 区域。