Neural Substrates of Electroacupuncture in Cardiovascular Control

电针控制心血管的神经基质

• 批准号: 8874256
• 负责人: John C Longhurst
• 金额: $ 38.05万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8874256
• 关键词: Abbreviations; Acupuncture Therapy; Acute; Adverse effects; American; Animals; Area; Automobile Driving; Biologic Characteristic; Blood Pressure; Brain; Cardiovascular system; Cell Nucleus; Cholecystokinin A Receptor; Cholecystokinin Receptor; Clinical; Conscious; Data; Disease; Electroacupuncture; Endorphins; Enkephalins; Figs - dietary; Genes; Glutamates; Goals; Grant; Hour; Hypertension; Hypotension; Hypothalamic structure; Incidence; Investigation; Knowledge; Medical; Messenger RNA; Methods; Midbrain structure; Modality; Modeling; Molecular; Morbidity - disease rate; Myocardial Ischemia; National Center for Complementary and Alternative Medicine; National Heart, Lung, and Blood Institute; Neurons; Neurotransmitters; Opioid; Oranges; Pathway interactions; Patients; Physicians; Physiological; Play; Population; Pro-Opiomelanocortin; Process; Production; Rattus; Reflex action; Regulation; Research; Role; Spinal Cord; Standardization; Structure of nucleus infundibularis hypothalami; Tetragastrin; Text; Thoracic spinal cord structure; Treatment Protocols; Visceral; Whole Organism; aged; blood pressure reduction; blood pressure regulation; hemodynamics; hypertension treatment; improved; individualized medicine; insight; mRNA Expression; midbrain central gray substance; mortality; neuromechanism; neurophysiology; neuroregulation; paraventricular nucleus; preproenkephalin; raphe nuclei; relating to nervous system; response

DESCRIPTION (provided by applicant): We have investigated the mechanisms by which acupuncture, particularly electroacupuncture (EA) regulates blood pressure (BP). EA has the capability to lower elevated BP and to alleviate demand-induced myocardial ischemia. Its actions are slow in onset but its duration of action is prolonged. Approximately 70% of experimental subjects with acute reflex-induced elevations in BP respond to EA. The most recent grant has focused on a long-loop pathway extending from the hypothalamic arcuate nucleus to the midbrain ventrolateral periaqueductal gray (vlPAG) to the medullary midline nucleus raphe' pallidus (NRP) and then the rostral ventrolateral medulla (rVLM) where the activity of premotor sympathetic neurons is inhibited by EA. We specifically identified a reinforcing reciprocating network between the arcuate and the vlPAG that serves to prolong the action of EA. We also defined an important role for the NRP as a nucleus that processes glutamatergic input from the vlPAG and through a 5-HT1A rVLM mechanism modulates sympathetic outflow. The central hypothesis of this competitive renewal is that a standardized course of acupuncture treatment and established methods convert nonresponders to responders to increase EA's efficacy in reducing elevated blood pressure (BP), particularly through its inhibitory action in the hypothalamic paraventricular nucleus (PVN). The present grant will focus on four new areas: 1) the role of the PVN modulated during EA by opioid (enkephalin and endorphinergic) inputs from the arcuate and through projections to the rVLM and IML inhibits reflex-evoked sympathetic activation, 2) the mechanism through which repetitive EA in conscious cold-induced hypertensive (CI-HTN) rats lowers BP, 3) transcriptional mechanisms regulating enkephalin and endorphin production in the rVLM and arcuate during repetitive stimulation in EA's action to lower BP in CI-HTN rats and 4) cholecystokinin neuromodulation of opioid activity in the PVN of animals unresponsive to the actions of EA. Anatomical, physiological, electrophysiological, pharmacological and molecular approaches will be used in the proposed studies that are highly relevant to patients that have the potential to benefit from clinical acupuncture.

描述（由申请人提供）：我们研究了针灸，特别是电针（EA）调节血压（BP）的机制。 EA 能够降低升高的血压并缓解需求引起的心肌缺血。其作用起效缓慢，但作用持续时间较长。大约 70% 的急性反射诱发血压升高的实验对象对 EA 有反应。最近的资助重点关注从下丘脑弓状核延伸到中脑腹外侧导水管周围灰质（vlPAG）再到髓质中线中缝苍白核（NRP），然后延伸到延髓头侧腹外侧（rVLM）的长环通路，其中活性EA 抑制运动前交感神经元的活性。我们特别确定了弓形和 vlPAG 之间的加强往复网络，用于延长 EA 的作用。我们还定义了 NRP 的重要作用，即处理来自 vlPAG 的谷氨酸输入并通过 5-HT1A rVLM 机制调节交感神经流出的细胞核。这种竞争性更新的核心假设是，针灸治疗的标准化疗程和既定方法可以将无反应者转变为有反应者，以提高 EA 在降低高血压 (BP) 方面的功效，特别是通过其对下丘脑室旁核 (PVN) 的抑制作用。目前的拨款将重点关注四个新领域：1) 在 EA 期间，PVN 通过来自弓形的阿片类药物（脑啡肽和内啡肽）输入调节，并通过投射到 rVLM 和 IML 抑制反射诱发的交感神经激活，2) 机制通过重复电针对清醒的冷诱发高血压 (CI-HTN) 大鼠降低血压，3) 调节脑啡肽的转录机制电针重复刺激 CI-HTN 大鼠降低血压期间 rVLM 和弓状体中内啡肽的产生，以及 4) 对 EA 作用无反应的动物 PVN 中阿片类药物活性的胆囊收缩素神经调节。解剖学、生理学、电生理学、药理学和分子方法将用于拟议的研究，这些研究与有可能从临床针灸中受益的患者高度相关。