CARDIOVASCULAR RESPONSE TO GLUTAMATE NITRIC OXIDE

对谷氨酸一氧化氮的心血管反应

• 批准号: 6330147
• 负责人: William Temple Talman
• 金额: $ 18万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-15 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330147
• 关键词: biological signal transduction; cardiovascular function; cyclic GMP; free radical scavengers; glutamates; immunocytochemistry; immunoelectron microscopy; laboratory rat; luminescence; microinjections; neural transmission; neurochemistry; neuroregulation; nitric oxide; solitary tract nucleus

The nucleus tractus solitarii (NTS) plays a critical role in cardio- vascular regulation. Glutamate (GLU) is a putative neurotransmitter in cardiovascular regions of the NTS where nitric oxide (NO) or nitrosyl factors elicit cardiovascular responses similar to those produced by GLU. Activation of GLU receptors at other central sites has been shown to cause release of NO, but studies have not been done to determine if GLU influences NO in NTS and, if so, if NO contributes to responses to GLU. Preliminary data suggest that GLU and NO containing nerves lie in close proximity in NTS and that inhibition of synthesis of NO by local neurons attenuates responses to GLU. The hypothesis of the current study is that responses to GLU in NTS are linked to NO. There are four specific aims. The first aim is to determine if NO participates in mediating cardiovascular effects produced by GLU receptor agonists in the NTS. Pharmacological studies will assess cardiovascular responses to injection of GLU agonists into the NTS of awake, unrestrained rats both before and after injection at the same site of reduced hemoglobin, a scavenger of NO; an inhibitor of neuronal NO synthase; L-arginine, the precursor of NO; or a donor of NO The second aim is to determine if NO is released from the NTS exposed to GLU receptor agonists. This in vitro neurochemical study will utilize freshly prepared tissue from NTS dissected from slices of rat brain stem and will measure NO by the chemiluminescence method. The third aim is to determine if effects of GLU on soluble guanylate cyclase are mediated through NO. An in vivo study will determine if blockade of soluble guanylate cyclase, an important step in signal transduction mediated by NO, alters responses to GLU microinjected into the NTS of awake rats. An in vitro study will directly assess effects of GLU on formation of cyclic GMP and will study the role of NO in producing those effects. The fourth aim is to determine the anatomical relationship between GLU terminals and neuronal elements that contain NO synthase (NOS) in the NTS. These studies will be important in expanding our understanding a) interrelationships between two putative transmitters in the NTS, b) the role of NO or nitrosyl factors in generating cardiovascular responses from NTS and c) cardiovascular influences of NTS in awake animals.

孤束核（NTS）在心血管系统中起着重要作用。 血管调节 谷氨酸（GLU）是一种公认的神经递质， NTS的心血管区域，其中一氧化氮（NO）或亚硝酰基 这些因素引起的心血管反应类似于 葡萄糖。 已显示在其他中心位点的GLU受体活化 导致NO的释放，但尚未进行研究以确定是否 GLU影响NTS中的NO，如果是这样，如果NO有助于对 葡萄糖。 初步数据表明，含GLU和NO的神经位于 近距离接触和局部抑制NO合成 神经元减弱对GLU的反应。本研究的假设 NTS中对GLU的反应与NO有关。 具体目标。 第一个目标是确定NO是否参与 介导GLU受体激动剂产生的心血管效应， 的NTS。药理学研究将评估心血管反应 将GLU激动剂注射到清醒的未受约束的大鼠的NTS中 在血红蛋白减少的相同部位注射之前和之后， NO清除剂;神经元NO合酶抑制剂; L-精氨酸， NO的前体;或NO的供体第二个目的是确定NO是否 从暴露于GLU受体激动剂的NTS中释放。 这 体外神经化学研究将使用NTS新鲜制备的组织 从大鼠脑干切片中解剖，并将通过 化学发光法 第三个目标是确定是否影响 在体内，GLU对可溶性鸟苷酸环化酶的作用是通过NO. 研究将确定是否阻断可溶性鸟苷酸环化酶， NO介导的信号转导的重要步骤改变了反应 将GLU微量注射到清醒大鼠的NTS中。 体外研究将 直接评估GLU对环GMP形成的影响，并将研究 NO在产生这些效应中的作用。 第四个目标是 确定GLU终末和神经元之间的解剖关系 在NTS中含有NO合酶（NOS）的元件。这些研究将 对扩大我们的理解很重要a）相互关系 B）NO或NO-1的作用， 亚硝酰基因子在由NTS产生心血管反应中的作用和c） NTS在清醒动物中的心血管影响。