SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

我们的部门开发和应用评估功能的方法， 中枢和外周儿茶酚胺能系统和协调 这些系统与其他稳态系统在健康，压力， 疾病本年度的研究成果包括：（1）正电子发射断层扫描 (PET)全身给予6-[18 F]氟多巴胺后扫描 [18F]-6 F-DA提供了一种非侵入性的体内方法来检查心脏 人类的交感神经支配和功能， 辐射剂量。(2)临床显微神经摄影和神经化学方法 用于证明糖皮质激素诱导的交感神经抑制， 人类，描述一个独特的神经化学模式在门克斯 疾病，以定位交感神经效应器功能障碍的部位 在多系统萎缩，以确定是否与法布里的患者 疾病有交感神经病变，以检验“肾上腺素假说” 的交感神经传递，以记录氯氮平引起的 去甲肾上腺素能刺激，并测试功能性 交感神经末梢上的β-肾上腺素受体和血管紧张素II受体 在人的前臂。(3)测定血浆O-甲基化 开发并验证了儿茶酚胺的代谢物， 发现测量血浆变肾上腺素水平可以提供 诊断嗜铬细胞瘤的上级神经化学方法， 儿茶酚胺分泌瘤(4)全面衡量 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的代谢 羊肺中的儿茶酚胺生物合成。肾脏DOPA~DA系统 另一种“非典型”的儿茶酚胺能系统， 盐敏感性高血压时该系统功能异常， 探索，以及治疗与左旋多巴作为肾多巴胺能 充血性心力衰竭的前药。

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.