Cytokine and sympathetic drive in heart failure

心力衰竭中的细胞因子和交感神经驱动

基本信息

  • 批准号:
    6704843
  • 负责人:
  • 金额:
    $ 5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-01-21 至 2007-12-31
  • 项目状态:
    已结题

项目摘要

Immune system activation (ISA) is a commonly recognized component of the heart failure syndrome. The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-lbeta)- the blood borne products of ISA- activate the sympathetic nervous system. The overall hypothesis of this project is that these pro-inflammatory cytokines contribute to the augmented sympathetic drive in heart failure by their actions upon neurons in the paraventricular nucleus (PVN) of the hypothalamus. Two principal mechanisms for this proposed effect will be investigated. 1) Circulating cytokines induce catecholamine release in PVN. Increased catecholamine content in PVN has been associated with heightened sympathetic drive in other pathophysiologicalconditions, such as neurogenic hypertension, that are also characterized by increased activity of the renin-angiotensinsystem (RAS). The present studies will examine the hypothesis that catecholamine release in PVN, induced by circulating cytokines, activates sympatho-excitatory PVN neurons, and that this effect is facilitated by interactions in PVN between catecholamines and the RAS. 2) Cytokines induce the production of reactive oxygen species (ROS). Cytokines may be produced in the brain, and may enter the brain via a saturable membrane transport system. The present studies will examine the hypothesisthat in heart failure the presence of cytokines in the PVN induces ROS, which activates sympatho-excitatory PVN neurons. Finally, these studies will examine the mechanisms by which activation of PVN neurons by circulating or intrinsic cytokines might elicit an increase in sympathetic drive. Recent evidence suggests that signals descending from PVN require activation of an angiotensin type 1 receptor in rostral ventrolateral medulla (RVLM) to effect an increase in sympathetic drive. The present studies will determine whether sympatho-excitatoryPVN neurons activated by pro-inflammatory cytokines utilize this pathway. Electrophysiologicalrecordingtechniques will be used in conjunction with push-pull analysis of peptide/transmitter release and immunohistochemistry to test these hypotheses in rats with ischemia-induced heart failure and in sham-operated controls. These studies will provide important new insightsinto the role of the pro-inflammatorycytokines in heart failure.
免疫系统激活(伊萨)是心力衰竭综合征的常见组成部分。 促炎性细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1 β(IL-1 β)-伊萨的血液传播产物-激活交感神经系统。 该项目的总体假设是,这些促炎细胞因子通过作用于下丘脑室旁核(PVN)中的神经元而有助于心力衰竭中增强的交感神经驱动。 两个主要机制,这一建议的效果将进行调查。1)循环细胞因子诱导室旁核释放儿茶酚胺。 室旁核中儿茶酚胺含量的增加与其他病理生理条件下交感神经驱动的增强有关,如神经源性高血压, 还以增强的肾素-血管紧张素系统(RAS)活性为特征。 目前的研究将检查的假设,即在PVN中,由循环细胞因子诱导的儿茶酚胺释放,激活交感神经兴奋性PVN神经元,这种效果是促进PVN之间的相互作用,儿茶酚胺和RAS。2)细胞因子诱导活性氧(ROS)的产生。 细胞因子可以在脑中产生,并且可以经由可饱和膜转运系统进入脑。 目前的研究将检验这一假设,即在心力衰竭中,PVN中细胞因子的存在诱导ROS,ROS激活交感兴奋性PVN神经元。 最后,这些研究将探讨 通过循环或内在细胞因子激活PVN神经元可能引起交感神经驱动增加的机制。最近的证据表明,从PVN下行的信号需要激活延髓头端腹外侧区(RVLM)的血管紧张素1型受体,以增加交感神经驱动。 目前的研究将确定是否交感兴奋PVN神经元激活的促炎细胞因子利用这一途径。电生理记录技术将与肽/递质释放的推拉分析和免疫组织化学结合使用,以在缺血诱导的心力衰竭大鼠和假手术对照组中检验这些假设。 这些研究将 为心力衰竭中促炎细胞因子的作用提供了重要的新见解。

项目成果

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Robert B Felder其他文献

Robert B Felder的其他文献

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{{ truncateString('Robert B Felder', 18)}}的其他基金

Brain MAP Kinases - Substrate for Sympathetic Excitation in Heart Failure
脑 MAP 激酶 - 心力衰竭交感神经兴奋的底物
  • 批准号:
    8204899
  • 财政年份:
    2010
  • 资助金额:
    $ 5万
  • 项目类别:
Brain MAP Kinases - Substrate for Sympathetic Excitation in Heart Failure
脑 MAP 激酶 - 心力衰竭交感神经兴奋的底物
  • 批准号:
    8399052
  • 财政年份:
    2010
  • 资助金额:
    $ 5万
  • 项目类别:
Brain MAP Kinases - Substrate for Sympathetic Excitation in Heart Failure
脑 MAP 激酶 - 心力衰竭交感神经兴奋的底物
  • 批准号:
    8038587
  • 财政年份:
    2010
  • 资助金额:
    $ 5万
  • 项目类别:
Brain MAP Kinases - Substrate for Sympathetic Excitation in Heart Failure
脑 MAP 激酶 - 心力衰竭交感神经兴奋的底物
  • 批准号:
    8589602
  • 财政年份:
    2010
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    8758110
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    6671631
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    8389884
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    8197258
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    7751935
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:
Cytokines and Sympathetic Activation in Heart Failure
心力衰竭中的细胞因子和交感神经激活
  • 批准号:
    7078626
  • 财政年份:
    2003
  • 资助金额:
    $ 5万
  • 项目类别:

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