Esler M D, Wallin G, Dorward P K, Eisenhofer G, Westerman R, Meredith I, Lambert G, Cox H S, Jennings G
Baker Medical Research Institute, Prahran, Victoria, Australia.
Am J Physiol. 1991 Apr;260(4 Pt 2):R817-23. doi: 10.1152/ajpregu.1991.260.4.R817.
In isolated organs, or when given in low dose intra-arterially, tricyclic antidepressant drugs are known to block reuptake of norepinephrine into sympathetic nerve varicosities, with a resultant increased norepinephrine washout. On the other hand, systemic administration of such drugs in humans reduces norepinephrine spillover to plasma. To clarify these seemingly contradictory findings, we have measured concurrently muscle sympathetic activity in the peroneal nerve (microneurography) and rates of norepinephrine spillover to plasma for the body as a whole and for the heart, the kidneys, and the forearm (radiotracer technique), both before and after intravenous infusion of desipramine, 0.5 mg/kg. Desipramine lowered the overflow of norepinephrine to plasma for the body as a whole and from the forearm and the kidneys (by 30-50%) but increased cardiac norepinephrine spillover by 25%. Both the number of sympathetic bursts per min in the peroneal nerve and their mean voltage amplitudes were markedly reduced after desipramine; total activity (bursts/min x mean burst amplitude) fell by approximately 90%. The effects of desipramine on norepinephrine spillover are explicable in terms of inhibition of central sympathetic outflow, balanced against the local blockade of transmitter reuptake. In most sites, the predominant effect is a reduction of norepinephrine overflow. For the heart, where reuptake is so important in transmitter disposition, the net effect is increased overflow.
在离体器官中，或者当以低剂量动脉内给药时，已知三环类抗抑郁药物会阻断去甲肾上腺素再摄取进入交感神经末梢，导致去甲肾上腺素清除增加。另一方面，在人体中全身给药这类药物会减少去甲肾上腺素向血浆中的溢出。为了阐明这些看似矛盾的发现，我们在静脉输注0.5mg/kg地昔帕明之前和之后，同时测量了腓总神经的肌肉交感神经活动（微神经ography）以及全身、心脏、肾脏和前臂的去甲肾上腺素向血浆中的溢出率（放射性示踪技术）。地昔帕明降低了全身以及前臂和肾脏的去甲肾上腺素向血浆中的溢出（降低30 - 50%），但使心脏去甲肾上腺素溢出增加了25%。地昔帕明给药后，腓总神经每分钟的交感神经冲动数量及其平均电压幅度均显著降低；总活动（冲动次数/分钟×平均冲动幅度）下降了约90%。地昔帕明对去甲肾上腺素溢出的影响可以用抑制中枢交感神经流出并与递质再摄取的局部阻断相平衡来解释。在大多数部位，主要作用是减少去甲肾上腺素溢出。对于心脏，再摄取在递质处置中非常重要，净效应是溢出增加。
