Bansinath M, Arbabha B, Turndorf H, Garg U C
Department of Anesthesiology, New York University Medical Center, NY 10016.
Neurochem Res. 1993 Oct;18(10):1063-6. doi: 10.1007/BF00966685.
N omega-nitro-L-arginine (NG-nitro-L-arginine) is a potent nitric oxide synthase inhibitor which crosses the blood brain barrier and does not undergo extensive metabolism in vivo. In this study, effect of chronic pretreatment of N omega-nitro-L-arginine (75 mg/kg, i.p., twice daily for 7 days) on the harmaline- (100 mg/kg, s.c.), picrotoxin- (4 mg/kg, s.c.), pentylenetetrazole- (50 mg/kg, i.p.), and L-glutamic acid- (400 micrograms/10 microliters/mouse, i.c.v.) induced increase in cerebellar cGMP was assessed. All the four drugs produced significant increase in cerebellar cGMP in vehicle pretreated control animals. Cerebellar cGMP increased induced by harmaline, picrotoxin, and L-glutamic acid was attenuated in N omega-nitro-L-arginine pretreated animals. These results indicate that in vivo cerebellar cGMP levels are increased by the prototype excitatory amino acid receptor agonist, L-glutamic acid and also by the drugs which augment the excitatory amino acid transmission. Furthermore, parenteral chronic administration of N omega-nitro-L-arginine blocks NO synthase in the brain and hence cerebellar cGMP response in chronic N omega-nitro-L-arginine treated animals could be used as a tool to assess the physiological functions of nitric oxide in vivo.
Nω-硝基-L-精氨酸是一种强效一氧化氮合酶抑制剂，它能穿过血脑屏障且在体内不会发生广泛代谢。在本研究中，评估了Nω-硝基-L-精氨酸（75毫克/千克，腹腔注射，每日两次，共7天）慢性预处理对由 harmaline（100毫克/千克，皮下注射）、印防己毒素（4毫克/千克，皮下注射）、戊四氮（50毫克/千克，腹腔注射）和L-谷氨酸（400微克/10微升/小鼠，脑室内注射）诱导的小脑环磷酸鸟苷（cGMP）增加的影响。在溶剂预处理的对照动物中，所有这四种药物均使小脑cGMP显著增加。在Nω-硝基-L-精氨酸预处理的动物中，由harmaline、印防己毒素和L-谷氨酸诱导的小脑cGMP增加被减弱。这些结果表明，在体内，原型兴奋性氨基酸受体激动剂L-谷氨酸以及增强兴奋性氨基酸传递的药物会使小脑cGMP水平升高。此外，Nω-硝基-L-精氨酸的肠胃外慢性给药会阻断大脑中的一氧化氮合酶，因此，在慢性Nω-硝基-L-精氨酸处理的动物中，小脑cGMP反应可作为评估体内一氧化氮生理功能的一种工具。
