Effect of Desipramine and Cocaine on Plasma Norepinephrine and Pressor Responses to Adrenergic Stimulation in Pithed Rats
Effect of Desipramine and Cocaine on Plasma Norepinephrine and Pressor Responses to Adrenergic Stimulation in Pithed Rats
复制标题
地昔帕明和可卡因对髓大鼠血浆去甲肾上腺素和肾上腺素能刺激的升压反应的影响
DOI：
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发表时间：
1983
影响因子：
2.9
通讯作者：
I. Kopin
中科院分区：
文献类型：
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作者：
M. Bayorh;Z. Żukowska;I. Kopin
摘要：交感神经元释放的去甲肾上腺素似乎作用于连接内的α1-肾上腺素受体，而给药的去甲肾上腺素主要作用于连接外的α2-肾上腺素受体。我们研究了去甲丙咪嗪抑制神经元摄取去甲肾上腺素的影响，（0.3毫克/千克，静脉注射）和可卡因（5 mg/kg iv）对去甲肾上腺素后去髓大鼠的升压作用和血浆去甲肾上腺素水平的影响（0.1、0.3和1.0 μg/kg iv）或在交感神经流出刺激期间（0.1、0.3和1.0 Hz，50 V，持续1分钟）。地昔帕明和可卡因增强去甲肾上腺素对心血管的作用比增强交感神经刺激的作用更大。去甲肾上腺素的血浆水平在交感神经刺激或静脉注射去甲肾上腺素后显着增加后，无论是去甲丙咪嗪或可卡因。交感神经刺激的心血管效应，而不是外源性去甲肾上腺素，肾上腺髓质切除大鼠相比，完整的大鼠减少。在肾上腺髓质切除大鼠中，地昔帕明增强了交感神经刺激期间的升压反应并增强了血浆去甲肾上腺素水平的增加，其程度与完整脊髓大鼠相同。通过摄取抑制给予的去甲肾上腺素的优先增强作用最可能是由于循环去甲肾上腺素对否则不可接近的连接内α1-肾上腺素受体的可及性增强。神经末梢区域中较高浓度的去甲肾上腺素通过突触前α2-肾上腺素受体的反馈抑制来限制神经递质的释放，从而通过对交感神经刺激的突触后反应的摄取抑制来掩盖增强作用。
Abstract: Sympathetic neuronally released norepinephrine appears to act at intrajunctional α1‐adrenoceptors, whereas administered norepinephrine acts mostly at extra‐junctional α2‐adrenoceptors. We examined the effects of inhibition of neuronal uptake of norepinephrine by desipramine (0.3 mg/kg iv) and cocaine (5 mg/kg iv) on the pressor effects and on plasma norepinephrine levels in pithed rats after the administration of norepinephrine (0.1, 0.3, and 1.0 μg/kg iv) or during stimulation of sympathetic outflow (0.1, 0.3, and 1.0 Hz at 50 V for 1 minute). Desipramine and cocaine potentiated the cardiovascular effects of administered norepinephrine to a greater extent than they potentiated the effects of sympathetic stimulation. Plasma levels of norepinephrine during sympathetic stimulation or after iv administration of norepinephrine were increased significantly after either desipramine or cocaine. The cardiovascular effects of sympathetic stimulation, but not of exogenous norepinephrine, were reduced in adrenomedullectomized rats compared to intact rats. In adrenomedullectomized rats, desipramine potentiates the pressor responses and enhances the increase in plasma norepinephrine levels during sympathetic stimulation to the same extent as in intact pithed rats. The preferential potentiation of administered norepinephrine by uptake inhibition is most likely due to enhancement of accessibility of circulating norepinephrine to otherwise inaccessible intrajunctional α1‐adrenoceptors. The higher concentrations of norepinephrine in the region of the nerve‐ending limit release of the neurotransmitter by feedback inhibition via presynaptic α2‐adrenoceptors, thereby masking potentiation by uptake inhibition of the postsynaptic responses to sympathetic stimulation.