Shibata S, Yamamoto Y, Tanaka T, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1995 Feb 6;273(3):223-8. doi: 10.1016/0014-2999(94)00678-z.
The effects of nitric oxide (NO) synthase inhibitors on the hypoxia/hypoglycemia-induced decrease in CA1 presynaptic fiber spikes elicited by stimulation of the Schaffer collaterals were investigated using rat hippocampal slices. Drugs were added to normal medium for 10 min before incubation under hypoxic/hypoglycemic conditions (15 min), and after a 3-h washout, the CA1 presynaptic potential was measured. Treatment with NG-nitro-L-arginine methyl ester but not with NG-nitro-D-arginine methyl ester produced a concentration-dependent attenuation of the hypoxia/hypoglycemia-induced decrease in presynaptic fiber spikes. In contrast, treatment with precursors of NO in the arginine-to-NO pathway, such as sodium nitroprusside, S-nitro-N-acetylpenicillamine and N-morpholino sydnonimine exacerbated the 15-min hypoxia/hypoglycemia-induced decrease in the CA1 presynaptic potential. The neuroprotective effect of NG-nitro-L-arginine methyl aster was significantly attenuated by co-treatment with L-arginine. The present results suggest a facilitatory role of NO production in hypoxia/hypoglycemia-induced presynaptic dysfunction in CA1 regions of hippocampal slices.
利用大鼠海马切片研究了一氧化氮（NO）合酶抑制剂对缺氧/低血糖诱导的、由刺激Schaffer侧支引发的CA1突触前纤维峰电位降低的影响。在缺氧/低血糖条件下孵育（15分钟）前10分钟，将药物添加到正常培养基中，在3小时洗脱后，测量CA1突触前电位。用NG-硝基-L-精氨酸甲酯处理而非用NG-硝基-D-精氨酸甲酯处理，可产生浓度依赖性地减弱缺氧/低血糖诱导的突触前纤维峰电位降低。相反，用精氨酸到NO途径中的NO前体处理，如硝普钠、S-硝基-N-乙酰青霉胺和N-吗啉代西多硝胺，会加剧15分钟缺氧/低血糖诱导的CA1突触前电位降低。与L-精氨酸共同处理可显著减弱NG-硝基-L-精氨酸甲酯的神经保护作用。目前的结果表明，在海马切片CA1区缺氧/低血糖诱导的突触前功能障碍中，NO生成起促进作用。
