Neural Substrates of Electroacupuncture in Cardiovascular Control

描述(申请人提供)：我们已经研究了针灸，特别是电针(EA)调节血压的机制。电针具有降低血压升高和减轻负荷所致心肌缺血的作用。其起效较慢，但持续时间较长。约70%患有急性反射引起的血压升高的实验受试者对电针有反应。最近的资助集中在从下丘脑弓状核到中脑导水管周围灰质腹外侧区(VlPAG)到中缝中线核(NRP)，然后是延髓吻侧腹外侧区(RVLM)的一条长环路上，在那里，运动前交感神经元的活动被电针抑制。我们特别确定了弓状核和vlPAG之间的一个加强的往复网络，它有助于延长电针的作用。我们还定义了NRP的重要作用，它是一个处理来自vlPAG的谷氨酸能输入的核，并通过5-HT1ARVLM机制调节交感神经流出。这种竞争性更新的中心假设是，标准化的针灸治疗过程和既定的方法将无效者转变为应答者，以增加电针在降低血压(BP)方面的有效性，特别是通过其在下丘脑室旁核(PVN)的抑制作用。目前的拨款将集中在四个新的领域：1)电针期间由弓状体类阿片(脑啡肽和内啡肽能)传入和向RVLM和IML投射调节PVN的作用抑制反射诱发的交感激活；2)清醒冷诱导高血压(CI-HTN)大鼠重复电针降低血压的机制；3)电针重复刺激时调节RVLM和弓状体内脑啡肽和内啡肽产生的转录机制；以及4)胆囊激肽对电针无反应动物PVN中阿片活性的神经调节作用。拟议的研究将使用解剖学、生理学、电生理学、药理学和分子方法，这些方法与有可能从临床针灸中受益的患者高度相关。

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.