Muscle Reflex Control of the Circulation

肌肉反射控制循环

• 批准号: 7072298
• 负责人: Lawrence I Sinoway
• 金额: $ 21.93万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-05 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072298
• 关键词: adenosine triphosphate; afferent nerve; blood circulation; blood flow measurement; blood pressure; cats; chloride channels; electromyography; electrophysiology; exercise; heart rate; microdialysis; muscle contraction; neuromuscular system; reflex; sympathetic nervous system

DESCRIPTION (provided by applicant): The long-range goal of the PI is to better understand mechanisms that control blood flow during exercise. The short-range goal of this proposal is to examine the role adenosine triphosphate (ATP) plays in evoking and modulating the pressor response to muscle contraction. The proposed experiments are based on recently published experiments from our laboratory as well as pilot data that have been gathered over the last year. We will evaluate three major aims: 1) we will examine the effects of muscle contraction on ATP release. We hypothesize that interstitial [ATP] rises with contraction. We will also examine whether ischemic and fatiguing contractions raise ATP and stimulate P2X receptors; 2) we will examine the ability of high levels of ATP per se to stimulate and sensitize the muscle reflex response to muscle contraction and stretch. We will raise interstitial ATP using an isolated hindlimb perfusion technique. ATP will be raised to levels seen during contraction. We hypothesize that raising interstitial ATP will evoke a pressor response (in the absence of stretch or contraction) but only at non-physiologic concentrations. We postulate that hindlimb perfusion at physiologic [ATP] will sensitize muscle afferents and increase the pressor response seen with muscle contraction and stretch; 3) We will examine the mechanisms by which ATP is released from skeletal muscle. Pilot data from our laboratory suggests that the skeletal muscle is the source of the increased interstitial ATP seen with contraction. We will examine the role played by skeletal muscle mechanosensitive channels, the role played by cystic fibrosis transmembrane conductance regulator (CFTR) channel, as well as the role played by exocytosis. To accomplish these goals we will employ a decerebrate cat model. In some studies muscle contraction and muscle stretch will be performed as skeletal muscle interstitial ATP is monitored via microdialysis. In other studies an isolated hindlimb perfusion technique will be used to selectively alter interstitial ATP concentration. Finally, we will perform studies in which we use the microdialysis method to deliver compounds in order to determine the mechanisms by which ATP is released from muscle cells. This work will provide new information on the mechanism by which blood pressure is regulated during exercise. This area is important for understanding exercise limitation in a variety of cardiovascular diseases.

描述（由申请人提供）：PI的远距离目标是更好地理解锻炼过程中控制血流的机制。该提案的短期目标是检查三磷酸腺苷（ATP）在唤起施加和调节肌肉收缩的反应中所发挥的作用。拟议的实验是基于我们实验室最近发表的实验以及去年收集的试验数据。我们将评估三个主要目标：1）我们将检查肌肉收缩对ATP释放的影响。我们假设该间隙[ATP]随着收缩而上升。我们还将检查缺血性和疲劳性收缩是否会增加ATP并刺激P2X受体； 2）我们将检查高水平的ATP本身刺激和敏感肌肉反应对肌肉收缩和拉伸的能力。我们将使用孤立的后肢灌注技术提高间质ATP。在收缩期间，ATP将提高到看到的水平。我们假设提高间质ATP会引起施加反应（在没有拉伸或收缩的情况下），但仅在非生理浓度下。我们假设生理学上的后肢灌注[ATP]将使肌肉传入敏感并增加肌肉收缩和拉伸的压力反应； 3）我们将检查从骨骼肌释放ATP的机制。我们实验室的试点数据表明，骨骼肌是收缩时观察到的间隙ATP增加的来源。我们将研究骨骼肌机械敏感通道的作用，骨骼肌机械敏感通道是囊性纤维化跨膜电导调节剂（CFTR）通道的作用，以及胞吐作用所起的作用。为了实现这些目标，我们将采用杂交猫模型。在一些研究中，将通过微透析监测骨骼肌间隙ATP，进行肌肉收缩和肌肉拉伸。在其他研究中，孤立的后肢灌注技术将用于选择性改变间质ATP浓度。最后，我们将进行研究，其中使用微透析方法传递化合物，以确定从肌肉细胞中释放ATP的机制。这项工作将提供有关运动过程中血压调节的机制的新信息。该领域对于理解各种心血管疾病的运动限制很重要。

项目成果

Central integration of muscle reflex and arterial baroreflex in midbrain periaqueductal gray: roles of GABA and NO.

中脑导水管周围灰质肌肉反射和动脉压力反射的中枢整合：GABA 和 NO 的作用。

• DOI: 10.1152/ajpheart.00163.2004
• 发表时间: 2004
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Li,Jianhua

Interstitial adenosine triphosphate modulates muscle afferent nerve-mediated pressor reflex.

• DOI: 10.1002/mus.21014
• 发表时间: 2008-08
• 期刊: MUSCLE & NERVE
• 影响因子: 3.4
• 作者: Li, Jianhua;Gao, Zhaohui;Kehoe, Valerie;Xing, Jihong;King, Nicholas;Sinoway, Lawrence
• 通讯作者: Sinoway, Lawrence

Spinal P2X receptor modulates muscle pressor reflex via glutamate.

• DOI: 10.1152/japplphysiol.90879.2008
• 发表时间: 2009-03
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: Jianhua Li;Jian Lu;Zhaohui Gao;S. Koba;Jihong Xing;Nicholas C. King;L. Sinoway

Aging augments interstitial K+ concentrations in active muscle of rats.

衰老会增加大鼠活动肌肉中的间质钾浓度。

• DOI: 10.1152/japplphysiol.00639.2005
• 发表时间: 2006
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Li,Jianhua;Sinoway,LawrenceI;Ng,Yuk-Chow
• 通讯作者: Ng,Yuk-Chow

Spinal P2X receptor modulates reflex pressor response to activation of muscle afferents.

脊髓 P2X 受体调节对肌肉传入神经激活的反射性升压反应。

• DOI: 10.1152/ajpheart.01095.2004
• 发表时间: 2005
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Gao,Zhaohui;Kehoe,Valerie;Sinoway,LawrenceI;Li,Jianhua
• 通讯作者: Li,Jianhua