Sympathetic denervation caused by long‐term noradrenaline infusions; prevention by desipramine and superoxide dismutase
Sympathetic denervation caused by long‐term noradrenaline infusions; prevention by desipramine and superoxide dismutase
复制标题
地昔帕明和超氧化物歧化酶预防长期输注去甲肾上腺素引起的交感神经支配；
DOI：
10.1111/j.1476-5381.1989.tb11928.x
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发表时间：
1989
影响因子：
7.3
通讯作者：
W. Osswald
中科院分区：
文献类型：
--
作者：
A. A. Teixeira;I. Azevedo;D. Branco;E. Rodrigues;W. Osswald
1观察正常犬侧隐静脉和对侧隐静脉连续静脉输注去甲肾上腺素（0.01和0.1 μg kg−1 h−1）的作用。采用Alzet渗透微型泵输注去甲肾上腺素、生理盐水、去甲肾上腺素+地西帕明或去甲肾上腺素+超氧化物歧化酶。2 .输注5天后，测定血浆和两隐静脉的去甲肾上腺素含量，并对静脉组织进行光镜形态测量和超微结构研究，并测定其O -甲基化能力（以[3H] -异丙肾上腺素为底物）。去甲肾上腺素对外侧隐静脉交感神经末梢造成剂量依赖性损伤。同时观察到神经元外结构和功能的改变（平滑肌细胞肥大、核畸形、血管壁增厚、O -甲基化能力受损）。去西帕明和超氧化物歧化酶能阻止或降低去甲肾上腺素对形态学和生化参数的影响；超氧化物歧化酶的保护作用比地西帕明更明显。结论是，中剂量的去甲肾上腺素发挥6 -羟多巴胺样作用，去西帕明或超氧化物歧化酶可部分或完全阻止这种化学交感神经切除术。数据表明，从去甲肾上腺素中提取的一种物质是导致所观察到的神经毒性作用的化学实体，它参与了自由基的形成，并受到神经元的吸收。
1 The effects of continuous intravenous infusion of noradrenaline (0.01 and 0.1 μg kg−1 h−1) were studied in both the infused lateral saphenous vein and the contralateral saphenous vein of normal dogs. Noradrenaline, saline, noradrenaline + desipramine or noradrenaline + superoxide dismutase were infused using Alzet osmotic minipumps. 2 After a 5 day infusion period, the noradrenaline content in plasma and in both saphenous veins was determined, and the venous tissues submitted to light microscope morphometry and ultrastructural study and used for the determination of their O‐methylation capacity (with [3H]‐isoprenaline as a substrate). 3 Noradrenaline caused dose‐dependent damage to the sympathetic nerve endings of the lateral saphenous veins. Concomitant changes in extraneuronal structure and function were observed (hypertrophy of smooth muscle cells, nuclear dismorphy, thickening of the vessel wall, impairment in O‐methylation capacity). 4 Desipramine and superoxide dismutase prevented or reduced the effects of noradrenaline on both the morphological and the biochemical parameters; the protection afforded by superoxide dismutase was more marked than that by desipramine. 5 It is concluded that moderately high doses of noradrenaline exert a 6‐hydroxydopamine‐like effect and that this chemical sympathectomy is partially or totally prevented by desipramine or superoxide dismutase. The data suggest that a substance derived from noradrenaline, in the formation of which free oxygen radicals are involved and which is subject to neuronal uptake, is the chemical entity responsible for the neurotoxic effect observed.