NITRIC OXIDE ON ACUPUNCTURE SIGNALS IN GRACILE NUCLEUS

一氧化氮对薄层核针灸信号的影响

• 批准号: 6089025
• 负责人: SHENG-XING MA
• 金额: $ 34.17万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-03 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6089025
• 关键词: acupuncture /acupressure; alternative medicine; arginine; brain stem; cardiovascular function; electrostimulus; fos protein; gamma aminobutyrate; laboratory rat; leg; neural inhibition; neural transmission; neurons; nitric oxide; nitric oxide synthase; sympathetic nervous system

Low-frequency electroacupuncture (EA) stimulation of hindlimb acupoints produces long-lasting sympathoinhibition in humans and rats. The gracile nucleus receives primary afferents projecting from the hindlimb, and stimulation of somatic sensory nerves results in changes in sympathetic nerve activity and arterial blood pressure. We have found that neuronal nitric oxide synthase (nNOS) expression in the gracile nucleus is markedly increased in old Fischer rats and reduced in spontaneously hypertensive rats. Our recent studies show that nNOS expression in the gracile nucleus is enhanced by low frequency EA applied to the hindlimb acupoints in rats accompanied by increase nNOS protein level. Preliminary results demonstrate that microinjection of either a nitric oxide (NO) donor or L-arginine into the gracile nucleus alters cardiovascular responses to EA stimulation of the acupoints. Spinothalamic tract cells located in the gracile nucleus are activated by a single electrical stimulus to the sciatic nerve while synaptic transmission through the dorsal column is depressed by a gamma-aminobutyric acid (GABA)-mediated depolarization of the gracile afferents. The purpose of the proposed research is to study our hypotheses that EA stimulation of hindlimb acupoints induces up-regulation of nNOS expression in the gracile nucleus, and the nNOS-NO-GABA system acts as an inhibitory modulation of cardiovascular functions in the gracile-thalamic pathways. The major aims are to determine: 1) Does NO in the gracile nucleus modify the sympatho- and cardiovascular responses to EA applied to the hindlimb acupoints? 2) Does GABAergic transmission mediate the inhibitory responses of NO on EA stimulation in the gracile nucleus? 3) Do time- and concentration-responses to EA-induced endogenous NO release in the gracile nucleus parallel the sympatho- and cardiovascular responses? 4) Is nNOS expression in the gracile nucleus selectively up-regulated by the EA? And 5) What are the distributions of Fos/nNOS expression in the gracile-thalamic pathways induced by the EA? The physiological recordings of arterial blood pressure, heart rate, and renal sympathetic nerve activity will incorporate with EA stimulation and neuropharmacological manipulations and histochemical studies to test the hypotheses in rat models. The results should advance our understanding of the sites and influences of low-frequency EA applied to the hindlimb acupoints on nNOS regulation in the gracile nucleus, and yield new insights regarding central mechanisms of NO and EA on sympathoinhibition.

低频电针（EA）刺激后肢 穴位在人和大鼠中产生持久的交感神经抑制作用。这 gracile核接收从后肢投射的主要传入， 刺激躯体感觉神经会导致交感神经的变化 活性和动脉血压。我们发现神经元一氧化氮 在旧核中的合成酶（NNOS）表达在旧的核中明显增加 Fischer大鼠自发性高血压大鼠减少。我们最近的研究 表明在低频中增强了格丝核中的nNOS表达 EA适用于大鼠的后肢穴位，并伴随着nnos的增加 蛋白质水平。初步结果表明，任何一个A 一氧化氮（NO）供体或L-精氨酸进入格拉丝核的变化 心血管对EA刺激穴位的反应。脊柱丘脑 位于格拉丝核中的道细胞被单个电气激活 刺激坐骨神经，同时突触通过背侧传播 色谱柱被γ-氨基丁酸（GABA）介导的去极化降低 Gracile传入。 拟议研究的目的是研究我们的假设 刺激后肢穴位诱导NNOS表达的上调 gracile核和nnos-no-gaba系统充当抑制 在脊柱 - 丘脑途径中的心血管功能的调节。这 主要目的是确定：1​​）在格拉丝核中不适合修改 对EA的交感神经和心血管反应应用于后肢穴位？ 2）GABA能传播是否介导了NO的抑制作用反应 刺激核核？ 3）将时间和浓度响应做到 EA诱导的内源性无释放在尖核中，相似 和心血管反应？ 4）是格丝核中的nNOS表达 由EA选择性上调？ 5）什么是 EA诱导的gracile-腹膜途径中的FOS/NNOS表达？这 动脉血压，心率和肾脏的生理记录 交感神经活动将与EA刺激和 神经药理操纵和组织化学研究以测试 大鼠模型中的假设。 结果应提高我们对站点和影响的理解 低频EA适用于在nnos调节中的后肢驱动器 格拉西核，并就NO和NO的中心机制产生新的见解 EA同情抑制。