Mechanisms of CNS Autonomic Regulation by Acupuncture

针灸调节中枢神经系统自主神经的机制

• 批准号: 9243979
• 负责人: Zhi-Ling Guo
• 金额: $ 34.76万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243979
• 关键词: Acupuncture Points; Acupuncture Therapy; Acute; Adenosine; Adenosine A1 Receptor; Adverse effects; American; Anatomy; Aneurysm; Antihypertensive Agents; Area; Attenuated; Axon; Biochemical; Blood Pressure; Brain Stem; Butyric Acids; Cardiovascular Physiology; Cardiovascular system; Cell Nucleus; Cephalic; Chemicals; Chronic; Clinical; Coronary Arteriosclerosis; Data; Disease; Ear; Ear Acupuncture; Electric Stimulation; Electroacupuncture; Electrophysiology (science); Enkephalins; Essential Hypertension; Fiber; Funding; Grant; Heart; Heart failure; Hyperactive behavior; Hypertension; Hypothalamic structure; Incidence; Knowledge; Location; Manuals; Mechanical Stimulation; Mechanics; Mediating; Mediation; Medical; Midbrain structure; Modality; Modeling; Molecular; Morbidity - disease rate; Myocardial Ischemia; Nerve; Nerve Fibers; Neuromodulator; Neurotransmitters; Nucleus solitarius; Opioid; Opioid Receptor; Patients; Peripheral; Pharmacology; Physicians; Physiological; Purinoceptor; Rattus; Reflex action; Regulation; Role; Rupture; Sensory; Sensory Receptors; Spinal Ganglia; Stroke; Thinness; United States National Institutes of Health; Vanilloid; afferent nerve; aged; blood pressure reduction; clinical practice; gamma-Aminobutyric Acid; hypertension treatment; improved; insight; mortality; neuromechanism; novel; public health relevance; receptor; response; somatic afferent nerve

 DESCRIPTION (provided by applicant): We are investigating mechanisms by which acupuncture regulates cardiovascular function, focusing on its modulation of elevated blood pressure (BP). Electroacupuncture (EA) is capable of lowering acute and chronic elevations in BP and alleviating demand-induced myocardial ischemia. Acupuncture's actions are slow in onset, but the duration of action is prolonged. We have been funded previously to study neural mechanisms underlying acupuncture's cardiovascular effects. Although these studies have shown that both EA and manual acupuncture (MA) applied at acupoints overlying somatic afferent nerves attenuate cardiovascular sympathoexcitatory responses, the mechanisms by which various forms of acupuncture application activate sensory nerve fibers to lower elevated BP are largely unknown. In this regard, although EA and MA activate sensory nerves through electrical and mechanical stimulation, it is unclear whether these modalities stimulate sensory afferent nerves and their perikarya in dorsal root ganglia through direct depolarization of fibers in passage or through a chemical intermediate mediated by a receptor specific mechanism, such as transient receptor potential vanilloid type-1 (TRPV1) or ATP purinergic receptors. Our studies also have demonstrated that, following stimulation of sensory nerves, EA lowers reflex elevations in BP through opioids by modulating presympathetic activity in the rostral ventrolateral medulla (rVLM), a brain stem nucleus that importantly controls sympathetic outflow and hence cardiovascular function. However, it is unclear if opioids act alone or mediate the actions of other cardiovascular-suppressing neuromodulators like adenosine or γ-amino butyric acid (GABA) to facilitate the action of acupuncture in lowering elevated BP during cardiovascular excitatory responses as well in sustained hypertension. Additionally, there is no information available on the role of opioids and other neurotransmitters in lowering elevated BP with acupuncture applied at locations other than somatic acupoints, like auricular acupuncture (AA). In this respect, manual and electrical AA applied at "the heart point" in the ear, which likey activates vagal afferent nerves projecting to the medulla, is used empirically to manage elevated BP. However, medullary mechanisms underlying AA's hypotensive actions remain unknown. The central hypothesis of this application is that acupuncture at somatic and cranial vagal nerve acupoints lowers elevated BP by modulating rVLM presympathetic activity through opioid- mediated mechanisms, by stimulating sensory receptors (MA) or thin fiber axons in passage (EA). The present grant focuses on four new areas: 1) electrical and mechanical-chemical sensory neural mechanisms by which EA and MA inhibit cardiovascular function; 2) the role of rVLM adenosine in opioid mediation of acupuncture inhibition of excitatory cardiovascular reflex responses; 3) acupuncture's action in lowering BP in sustained hypertension through medullary enkephalins and adenosine and 4) medullary mechanisms of auricular acupuncture in modulating elevated BP through actions of opioids and GABA. Anatomical, biochemical, physiological, electrophysiological, pharmacological and molecular approaches will be used in the proposed studies that are highly relevant to patients with hypertension and sympathetic hyperactivity, who have the potential to benefit from clinical acupuncture.

 描述（由适用提供）：我们正在研究针灸调节心血管功能的机制，重点是调节其升高血压（BP）。电针（EA）能够降低BP的急性和慢性升高，并减轻需求引起的心肌缺血。针灸的动作发作缓慢，但动作的持续时间延长了。 We have been funded previously to study neural mechanisms underlying acupuncture's cardiovascular effects.Although these studies have shown that both EA and manual acupuncture (MA) applied at acupoints overlying somatic afferent nerves attenuate cardiovascular sympathoexcitatory responses, the mechanisms by which various forms of acupuncture application activate sensory nerve fibers to lower elevated BP are largely unknown.In this regard, although EA and MA activate sensory nerves through electrical and mechanical stimulation, it is unclear whether these modalities stimulate sensory afferent nerves and their perikarya in dorsal root ganglia through direct depolariation of fibers in passage or through a chemical intermediate mediated by a receptor specific mechanism, such as transient receptor potential vanilloid type-1 (TRPV1) or ATP purinergic receptors.我们的研究还表明，在刺激感觉神经之后，EA通过调节腹侧外侧髓质（RVLM）中的前交感神经来降低BP的反射升高，这是一种脑干核，这是一种重要的控制交感神经核，它可以控制交感神经的核能，从而可以控制性交感神经核。但是，目前尚不清楚阿片类药物是单独起作用还是介导其他心血管抑制神经调节剂（如腺苷或γ-氨基丁酸）（GABA）的作用，以促进在降低心血管兴奋期在降低BP升高的兴奋性兴奋性反应中的作用，并在持续性高压率降低心血管兴奋性反应中。此外，还没有有关阿片类药物和其他神经递质在降低BP升高BP中使用针灸（如耳尖）（例如耳孔针灸（AA））的作用的信息。在这方面，在耳朵中的“心脏点”上应用的手动和电气AA，就像激活投射到髓质的迷走神经传入神经一样，在经验上用于管理升高的BP。但是，AA降压作用的髓质机制尚不清楚。该应用的中心假设是，通过刺激通道中的感觉受体（MA）或薄纤维轴突来调节RVLM的PRESANEDTICT活性，从而降低了BP升高BP的针灸，通过刺激传播中的感觉受体（MA）或薄纤维轴突（EA）（EA）。目前的赠款侧重于四个新领域：1）EA和MA抑制心血管功能的电气和机械化学感觉神经元机制； 2）RVLM腺苷在兴奋性心血管反射反应的针灸抑制的阿片类药物介导中的作用； 3）针灸在通过髓样enkephalins和腺苷中降低持续高血压的BP的作用，以及4）髓质针灸通过阿片类药物和GABA的作用调节升高BP的髓质机制。解剖学，生化，生理学，电生理，药物学和分子方法将用于与高血压和交感神经过度活跃的患者高度相关的拟议研究中，这些患者有可能受益于临床针刺。