SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

健康和疾病中的交感肾上腺和儿茶酚胺能功能

• 批准号: 3760325
• 负责人: D S GOLDSTEIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3760325
• 关键词: Fabry's disease; Menkes' syndrome; alpha adrenergic receptor; angiotensin II; catecholamines; congestive heart failure; dopamine; heart disorder diagnosis; heart function; heart innervation; homeostasis; hormone receptor; human subject; hypertension; laboratory rat; neurochemistry; neurotransmitter biosynthesis; noninvasive diagnosis; norepinephrine; positron emission tomography; prodrugs; spontaneous hypertensive rat; stress; sympathetic nervous system

Our Section develops and applies methods for assessing the function of central and peripheral catecholaminergic systems and the coordination of these systems with other homeostatic systems in health, stress, and disease. Findings this year include: (1) positron emission tomographic (PET) scanning after systemic administration of 6-[18F]fluorodopamine ([18F]-6F-DA) provided a noninvasive, in vivo means to examine cardiac sympathetic innervation and function in humans, with acceptable absorbed radiation doses.(2) Clinical microneurographic and neurochemical methods were used to demonstrate gluco-corticoid-induced sympathoinhibition in humans, to describe a distinctive neurochemical pattern in Menkes disease, to localize the site of sympathetic neuroeffector dysfunction in multiple system atrophy, to determine whether patients with Fabry's disease have sympathetic neuropathy, to test the "epinephrine hypothesis" of sympathetic neurotransmission, to document clozapine~induced noradrenergic stimulation, and to test for the presence of functional beta-adrenoceptors and angiotensin II receptors on sympathetic terminals in the human forearm. (3) Assays for plasma levels of O~methylated metabolites of catecholamines were developed and validated, and measurements of plasma levels of metanephrines were found to provide superior neurochemical means to diagnose pheochromocytoma, a catecholamine-secreting tumor. (4) Comprehensive measurements of concentrations of norepinephrine and dopamine and their metabolites in swine and sheep provided evidence for substantial production and metabolism of dopamine in porcine mesenteric organs and for non~neuronal catecholamine biosynthesis in ovine lungs. The renal DOPA~DA system is another "atypical" catecholaminergic system, and the possibility of abnormal function of this system in salt~sensitive hypertension is being explored, as well as treatment with L~DOPA as a renal dopaminergic prodrug in congestive heart failure.

我们部门开发并应用评估功能的方法 中枢和外周儿茶酚胺能系统及其协调 这些系统与健康、压力和其他稳态系统 疾病。今年的研究结果包括：（1）正电子发射断层扫描 6-[18F]氟多巴胺全身给药后（PET）扫描 ([18F]-6F-DA) 提供了一种非侵入性体内检查心脏的方法 人类的交感神经支配和功能，具有可接受的吸收 辐射剂量。（2）临床显微神经造影和神经化学方法 用于证明糖皮质激素诱导的交感神经抑制 人类，描述门克斯独特的神经化学模式 疾病，定位交感神经效应器功能障碍的部位 在多系统萎缩中，确定患者是否患有法布里氏症 疾病有交感神经病变，要检验“肾上腺素假说” 交感神经传递，记录氯氮平诱导的 去甲肾上腺素能刺激，并测试功能性的存在 交感神经末梢上的 β-肾上腺素受体和血管紧张素 II 受体 在人类的前臂。 (3)血浆O~甲基化水平的测定 开发并验证了儿茶酚胺的代谢物，并且 发现血浆变肾上腺素水平的测量可以提供 诊断嗜铬细胞瘤的高级神经化学方法 分泌儿茶酚胺的肿瘤。 (4) 综合测量 去甲肾上腺素和多巴胺及其代谢物的浓度 猪和羊提供了大量生产的证据 多巴胺在猪肠系膜器官和非神经元代谢 绵羊肺中儿茶酚胺的生物合成。肾脏的 DOPA~DA 系统是 另一种“非典型”儿茶酚胺能系统，以及 盐敏感性高血压中该系统的功能异常正在被研究 探索，以及用左旋多巴作为肾多巴胺能治疗 充血性心力衰竭的前药。