SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

儿茶酚胺在正常生理、压力和疾病中是重要的。 肾上腺髓质激素和交感神经成分 交感肾上腺系统使用儿茶酚胺、肾上腺素（EPI）和 去甲肾上腺素（NE）作为主要效应生化物质。 的 多巴胺（DA）和去甲肾上腺素（NE）是重要的中枢神经递质。 神经传递素 在肾脏中，DA参与钠平衡。 我们的目标是：（1）了解交感肾上腺系统是如何 （2）与其他系统的功能相协调; 确定脑NE在神经内分泌应激表达中的作用 反应;和（3）确定异常肾多巴-DA功能的基础， 钠稳态失调，如盐敏感性高血压。 全身给药后的正电子发射断层扫描（PET） [18 F]-6-氟多巴（[18 F]-6 F-DA）的研究提供了第一个非侵入性， 体内方法检查心脏交感神经支配和功能 人类 一种多电极阵列电化学检测器（神经化学 分析仪）用于测定血浆和尿液中[18F]-6-DA的水平， 神经化学结果表明，[18F]-6-DA被摄取， 进入交感神经末梢并转化为氟化类似物 的NE。 交感神经直接记录与测量相结合 区域NE溢出被用来证明系统性 给药α 2-肾上腺素受体拮抗剂，育亨宾， 通过刺激交感神经流出增加NE释放， 阻断人类突触前α 2受体。在一个不同的子群中 原发性高血压、交感肾上腺高反应性 育亨宾激发试验表明。 在体微透析 大鼠表明，育亨宾释放NE进入动脉血浆， 脑细胞外液，高皮质醇血症废除 育亨宾诱导的NE在脑和外周中的释放。 进一步 内源性血浆多巴和 在大鼠中获得了儿茶酚胺生物合成，并且异常增加 多巴尿排泄和低尿DA：多巴比值被发现， 盐敏感性高血压患者。 PET扫描，神经化学 分析，微透析，直接交感神经记录，和 分子生物学技术将被用来阐明的作用， 健康、压力和疾病中的儿茶酚胺能系统。

Catecholamines are important in normal physiology, stress, and disease. The adrenomedullary hormonal and sympathetic neural components of the sympathoadrenal system use the catecholamines, epinephrine (EPI) and norepinephrine (NE) as the main effector biochemicals. The catecholamines dopamine (DA) and NE are important central neurotransmitters. In the kidney, DA participates in sodium balance. Our goals have been to: (1) understand how the sympathoadrenal system is regulated and its function coordinated with that of other systems; (2) determine the role of brain NE in the expression of neuroendocrine stress responses; and (3) identify bases for abnormal renal Dopa-DA function in disorders of sodium homeostasis such as salt-sensitive hypertension. Positron emission tomography (PET) scanning after systemic administration of [18F]-6-fluorodopamine ([18F]-6F-DA) provided the first noninvasive, in vivo means to examine cardiac sympathetic innervation and function in humans. A multielectrode array electrochemical detector (neurochemical analyzer) was used to assay plasma and urine levels of [18F]-6-DA in humans, and the neurochemical results indicated that [18F]-6-DA is taken up into sympathetic nerve endings and converted to the fluorinated analog of NE. Combined direct sympathetic nerve recording and measurement of regional NE spillover was used to demonstrate that systemic administration of the alpha2-adrenoceptor antagonist, yohimbine, increases NE release by both stimulating sympathoneural outflow and blocking presynaptic alpha2-receptors in humans. in a distinct subgroup of patients with essential hypertension, sympathoadrenal hyperreactivity was indicated by yohimbine challenge testing. In vivo microdialysis in rats showed that yohimbine releases NE into the arterial plasma and into brain extracellular fluid, and that hypercortisolemia abolishes yohimbine-induced release of NE in the brain and periphery. Further evidence for a relationship between endogenous plasma Dopa and catecholamine biosynthesis was obtained in rats, and abnormally increased urinary excretion of Dopa and a low urinary DA: Dopa ratio were found in patients with saltsensitive hypertension. PET scanning, neurochemical analysis, microdialysis, direct sympathetic nerve recording, and molecular biological techniques will be used to elucidate the roles of catecholaminergic systems in health, stress, and disease.