CARDIOVASCULAR RESPONSE TO GLUTAMATE NITRIC OXIDE

孤束核(NTS)在心脏活动中起着重要作用。 血管调节。谷氨酸(GLU)是一种可能的神经递质。 一氧化氮(NO)或亚硝基的NTS心血管区域 引起心血管反应的因素类似于 谷氨酸。其他中枢部位的GLU受体也被激活 导致NO的释放，但还没有研究确定 谷氨酸影响NTS中的NO，如果是这样，如果NO参与了对 谷氨酸。初步数据表明，GLU和NO的神经存在于 NTS亲和性与局部抑制NO合成 神经元减弱对GLU的反应。本研究的假设 NTS对GLU的反应与NO有关。一共有四个 明确的目标。第一个目标是确定是否没有人参与 GLU受体激动剂对大鼠心血管效应的影响 国家安全局。药理学研究将评估心血管反应 清醒大鼠孤束核注射GLU激动剂 在注射还原血红蛋白的同一部位前后， 一氧化氮合酶的清除剂；一氧化氮合酶的抑制剂；L-精氨酸， NO的前体；或NO的供体第二个目标是确定是否没有 是由暴露于GLU受体激动剂的NTS释放的。此入站 体外神经化学研究将利用NTS新鲜准备的组织 从大鼠脑干的切片中解剖出来，将通过 化学发光法。第三个目标是确定 可溶性鸟苷环化酶上的谷氨酸是通过NO介导的。一个活体内 研究将确定是否阻断可溶性鸟苷环化酶，以及 NO介导的信号转导的重要一步，改变反应 将GLU微量注射到清醒大鼠的NTS。一项体外研究将 直接评估GLU对环状GMP形成的影响并将进行研究 一氧化氮在产生这些效应中的作用。第四个目标是 确定GLU终末与神经元的解剖关系 NTS中不含合成酶(NOS)的元素。这些研究将 重要的是要扩大我们对a)相互关系的理解 在NTS中的两个假定的传递体之间，b)NO或 NTS和c)诱发心血管反应中的亚硝基因子 NTS对清醒动物心血管的影响。

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.