Johnson E M, O'Brien F
J Pharmacol Exp Ther. 1976 Jan;196(1):53-61.
The administration of guanethidine to adult rats has been shown by morphological criteria to destroy sympathetic neurons. The objective of this study was to evaluate by biochemical and functional criteria the degree and permanence of this sympathectomy. Young adult male rats (260-300 g) were injected with saline (controls) or with guanethidine for 5 weeks. The status of the sympathetic nervous system in the animals was evaluated 1, 3 and 6 to 7 months after cessation of treatment. Seven months after cessation of treatment; the activity of tyrosine hydroxylase in the superior cervical ganglia of treated animals was greatly reduced, as were the norepinephrine levels in peripheral tissues. The concentration of epinephrine and the activity of tyrosine hydroxylase in adrenals were not different from controls at any of the times studied. Norepinephrine concentrations in several areas of the central nervous system were unchanged. Increases in blood pressure in response to stimulation of the sympathetic vasomotor outflow in the pithed rat preparation were markedly and permanently reduced in guanethidine-treated animals. Isolated intestinal nerve-muscle preparations from guanethidine-treated animals usually contracted in response to nerve stimulation, rather than relaxing as in controls. The response to stimulation of the hypogastric nerve in vas deferens preparations was reduced 1 month after cessation of treatment. The responses of the vas deferens from guanethidine-treated and control animals were the same 7 months after treatment despite a 93% reduction in norepinephrine concentration. The data demonstrate that the administration of guanethidine to adult rats produces a marked and permanent destruction of the peripheral sympathetic nervous system.
形态学标准显示，给成年大鼠施用胍乙啶会破坏交感神经元。本研究的目的是通过生化和功能标准评估这种交感神经切除术的程度和持久性。将年轻成年雄性大鼠（260 - 300克）注射生理盐水（对照组）或胍乙啶，持续5周。在停止治疗后1、3和6至7个月评估动物交感神经系统的状态。停止治疗7个月后，治疗组动物颈上神经节中酪氨酸羟化酶的活性大大降低，外周组织中的去甲肾上腺素水平也降低。在所研究的任何时间，肾上腺中肾上腺素的浓度和酪氨酸羟化酶的活性与对照组无差异。中枢神经系统几个区域的去甲肾上腺素浓度未发生变化。在脊髓麻醉大鼠制备中，胍乙啶治疗组动物对交感缩血管传出神经刺激的血压升高反应明显且永久性降低。胍乙啶治疗组动物的离体肠神经 - 肌肉制剂通常对神经刺激产生收缩反应，而不像对照组那样松弛。停止治疗1个月后，输精管制剂对腹下神经刺激的反应降低。尽管去甲肾上腺素浓度降低了93%，但胍乙啶治疗组和对照组动物的输精管在治疗7个月后的反应相同。数据表明，给成年大鼠施用胍乙啶会导致外周交感神经系统明显且永久性的破坏。
