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.

后肢低频电针 (EA) 刺激 穴位对人类和大鼠产生持久的交感神经抑制作用。这 薄核接收从后肢投射的初级传入神经，并且 刺激躯体感觉神经导致交感神经发生变化 活动和动脉血压。我们发现神经元一氧化氮 老年人纤细核中合酶（nNOS）的表达显着增加 Fischer 大鼠和自发性高血压大鼠减少。我们最近的研究 表明低频增强了纤细核中 nNOS 的表达 电针刺激大鼠后肢穴位伴nNOS升高 蛋白质水平。初步结果表明显微注射 一氧化氮 (NO) 供体或 L-精氨酸进入纤细核改变 心血管对穴位电针刺激的反应。脊髓丘脑 位于薄核的束细胞被单一的电激活 刺激坐骨神经，同时突触通过背侧传递 柱被 γ-氨基丁酸 (GABA) 介导的去极化抑制 的纤细传入。 拟议研究的目的是研究我们的假设，即 EA 刺激后肢穴位可诱导 nNOS 表达上调 纤细核，nNOS-NO-GABA 系统起到抑制作用 薄层-丘脑通路中心血管功能的调节。这 主要目的是确定： 1) 纤细核中的 NO 是否会改变 后肢穴位电针的交感神经和心血管反应如何？ 2) GABA能传递是否介导NO对EA的抑制反应 薄核的刺激？ 3) 进行时间和浓度反应 EA 诱导的纤细核内源性 NO 释放与交感神经平行 和心血管反应？ 4) nNOS在纤细核中表达吗 由 EA 选择性上调？ 5) 的分布是什么 EA 诱导的纤薄-丘脑通路中 Fos/nNOS 表达？这 动脉血压、心率和肾功能的生理记录 交感神经活动将与 EA 刺激相结合 神经药理学操作和组织化学研究来测试 大鼠模型中的假设。 研究结果应该能增进我们对遗址及其影响的理解 低频 EA 应用于后肢穴位对 nNOS 调节的影响 纤细核，并对 NO 和的中心机制产生新的见解 EA 对交感神经抑制。