SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

儿茶酚胺在正常生理、压力和疾病中都很重要。 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)为主要效应生物化学物质。这个 儿茶酚胺、多巴胺和去甲肾上腺素是重要的中枢神经系统。 神经递质。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 规范的，与其他制度功能相协调的； 测定脑内去甲肾上腺素在神经内分泌应激表达中的作用 反应；以及(3)确定肾脏多巴-多巴胺功能异常的基础。 钠稳态失调，如盐敏感型高血压。 全身给药后的正电子发射断层扫描 [18F]-6-氟多胺([18F]-6F-DA)提供了第一个非侵入性， 在活体内意味着检查心脏交感神经的支配和功能 人类。一种多电极阵列电化学检测器(神经化学 分析仪)测定血浆和尿液中[18F]-6-DA水平。 神经化学结果表明，[18F]-6-DA被摄取 上升到交感神经末梢，并转化为氟化类似物 东北地区。交感神经直接记录联合测量 区域NE溢出被用来证明系统性的 注射α2肾上腺素能受体拮抗剂育亨宾， 刺激交感神经流出增加去甲肾上腺素释放 阻断人类突触前α2受体。在一个不同的子群中 高血压病患者交感-肾上腺高反应性 育亨宾挑战试验表明。体内微渗析的实验研究 大鼠显示育亨宾将去甲肾上腺素释放到动脉血浆和 脑细胞外液，这种高皮质醇血症可以消除 育亨宾诱导脑和外周NE释放。进一步 内源性血浆多巴与多巴关系的证据 大鼠体内儿茶酚胺的生物合成异常增加 尿多巴排泄量和尿多巴胺/多巴比值较低。 盐敏感型高血压患者。PET扫描，神经化学检查 分析，微透析，直接交感神经记录，以及 分子生物学技术将被用来阐明 儿茶酚胺能系统与健康、压力和疾病。

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.