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Cardiovascular Response to Glutamate Nitric Oxide

对谷氨酸一氧化氮的心血管反应

基本信息

批准号：
7095191
负责人：
William Temple Talman
金额：
$ 21.53万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-12-15 至 2009-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): We have localized immunoreactivity for neuronal nitric oxide synthase, glutamate, NMDAR1 receptor subunits, and GLUR1 receptor subunits in the nucleus tractus solitarii (NTS) of rats and have identified strong associations between glutamate and nNOS and between each of the receptor types and nNOS in NTS. Our pharmacological studies suggest that responses to activation of glutamate receptors in NTS represent integrated action dependent on a link between ionotropic glutamate receptor and nitric oxide mechanisms in the NTS. The current protocols utilize immunohistochemical light, confocal and electron microscopic techniques and pharmacological methods to test the hypothesis that baroreflex transmission through ionotropic glutamate receptors in the nucleus tractus solitarii depends on neuronal nitric oxide synthase and soluble guanylate cyclase. There are two multifaceted specific aims. First we seek to define physiological and anatomical relationships between glutamatergic baroreceptor transmission and nNOS in NTS. Second, we seek to define physiological and anatomical relationships between glutamate receptors and cyclic GMP in NTS. We anticipate these studies will demonstrate that cardiovascular responses elicited by activation of NMDA and non-NMDA ionotropic glutamate receptors in NTS will depend to a significant degree on an intact nitroxidergic system in NTS, that responses will be attenuated or lost with interruption of the latter system, and that baroreflexes will be attenuated by interruption of nitric oxide synthesis or transduction of nitric oxide signals through soluble guanylate cyclase. We anticipate that our anatomical studies will show, at the electron micrsocopic level, that ionotropic glutamate receptors are frequently associated with nNOS and soluble guanylate cyclase immunoreactivity. Metabotropic receptors may be similarly associated, but at the electron microscopic level we expect to find that the latter receptors lie presynaptically with respect to nNOS neurons while the former predominantly occur postsynaptically, i.e. on nNOS immunoreactive dendrites or neurons in NTS.

描述（由申请人提供）：我们在大鼠孤立束核（NTS）中发现了神经元一氧化氮合酶、谷氨酸、NMDAR1受体亚基和GLUR1受体亚基的局部免疫反应性，并确定了谷氨酸和nNOS之间以及NTS中每种受体类型和nNOS之间的强关联。我们的药理学研究表明，NTS中对谷氨酸受体激活的反应代表了依赖于NTS中嗜离子性谷氨酸受体和一氧化氮机制之间联系的综合作用。目前的方案利用免疫组织化学光、共聚焦和电子显微镜技术以及药理学方法来验证孤独束核中通过嗜离子性谷氨酸受体的压力反射传递依赖于神经元一氧化氮合酶和可溶性鸟苷酸环化酶的假设。有两个多方面的具体目标。首先，我们试图定义NTS中谷氨酸压力感受器传递与nNOS之间的生理和解剖关系。其次，我们试图确定NTS中谷氨酸受体和环GMP之间的生理和解剖关系。我们预计这些研究将证明NTS中NMDA和非NMDA嗜离子性谷氨酸受体的激活所引起的心血管反应将在很大程度上取决于NTS中完整的氮氧能系统，该反应将随着后一系统的中断而减弱或消失，并且压力反射将因一氧化氮合成或通过可溶性鸟苷酸环化酶转导一氧化氮信号的中断而减弱。我们预计我们的解剖研究将在电子显微镜水平上显示，嗜离子性谷氨酸受体经常与nNOS和可溶性鸟苷酸环化酶的免疫反应性相关。代谢受体可能也有类似的关联，但在电子显微镜下，我们期望发现后者受体位于nNOS神经元的突触前，而前者主要发生在突触后，即NTS的nNOS免疫反应性树突或神经元上。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

NO and central cardiovascular control: a simple molecule with a complex story.

DOI：
10.1161/01.hyp.0000238142.22799.80
发表时间：
2006-10
期刊：
Hypertension
影响因子：
8.3
作者：
W. Talman
通讯作者：
W. Talman

Evidence for a glutamatergic input to pontine preganglionic neurons of the superior salivatory nucleus in rat.

大鼠上唾液核的脑桥节前神经元有谷氨酸能输入的证据。

DOI：
10.1016/s0891-0618(03)00033-4
发表时间：
2003
期刊：
Journal of chemical neuroanatomy
影响因子：
2.8
作者：
Lin,LiHsien;Agassandian,Khristofor;Fujiyama,Fumino;Kaneko,Taneshi;Talman,WilliamT
通讯作者：
Talman,WilliamT

Nitroxidergic innervation of human cerebral arteries.

人脑动脉的氮氧化能神经支配。

DOI：
10.1016/j.autneu.2010.04.012
发表时间：
2010
期刊：
Autonomic neuroscience : basic & clinical
影响因子：
0
作者：
Taktakishvili,OtarM;Lin,Li-Hsien;Vanderheyden,AndrewD;Nashelsky,MarcusB;Talman,WilliamT
通讯作者：
Talman,WilliamT

Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii.