Petersen J S, Liu W, Kapusta D R, Varner K J
Department of Pharmacology, Panum Institute, University of Copenhagen, Denmark.
Hypertension. 1997 May;29(5):1173-7. doi: 10.1161/01.hyp.29.5.1173.
Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.
静脉注射抗高血糖药物二甲双胍可降低动脉血压和交感神经活性（SNA）。为了验证二甲双胍通过中断神经节神经传递来抑制SNA这一假说，我们比较了静脉注射二甲双胍和神经节阻滞剂三甲噻芬对戊巴比妥麻醉的雄性Sprague-Dawley大鼠节后肾神经和节前肾上腺交感神经的作用。静脉注射二甲双胍可引起节后肾SNA剂量依赖性降低（1mg/kg：0±0%；10mg/kg：-20±4%；100mg/kg：-92±3%；n = 7）。相反，只有最大剂量的二甲双胍影响节前肾上腺SNA（100mg/kg：肾上腺SNA变化量=-14±6%；n = 8）。静脉注射三甲噻芬（5mg/kg）进行神经节阻断产生了与高剂量二甲双胍后观察到的反应相似的差异性交感抑制反应（肾SNA变化量=-100±3%；肾上腺SNA变化量=-17±7%；P <.001）。在静脉注射二甲双胍引起的交感抑制反应高峰期之前和期间，在脊髓中对节前肾神经元进行电刺激，并比较刺激诱发的节后肾SNA增加幅度。二甲双胍剂量依赖性地减弱了脊髓刺激引起的节后肾SNA增加幅度（30mg/kg：-23±8%；90mg/kg：-65±11%；270mg/kg：-91±8%；每个剂量n = 6）。我们得出结论，高剂量静脉注射二甲双胍会中断肾神经中的神经节神经传递。
