Takeuchi K, Ohuchi T, Miyake H, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
J Pharmacol Exp Ther. 1993 Sep;266(3):1512-9.
The role of nitric oxide (NO) in the regulation of gastroduodenal HCO3- secretion was investigated in anesthetized rats using the NO biosynthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME). HCO3- secretion was measured at pH 7.0 using a pH-stat method in the chambered stomach in the presence of omeprazole or in the proximal duodenum. Intravenous administration of L-NAME (1-5 mg/kg) increased HCO3- secretion in a dose-dependent manner in both the stomach and duodenum, with a concomitant elevation of arterial blood pressure. The stimulatory effect of L-NAME on HCO3- secretion was mimicked by another NO synthase inhibitor, NG-monomethyl-L-arginine (50 mg/kg), but not by the enantiomer NG-nitro-D-arginine methyl ester, and was significantly antagonized by concurrent administration of L-arginine, but not D-arginine, at 200 mg/kg. The exogenous NO donor nitroprusside (4 mg/kg) by itself decreased the rate of HCO3- secretion and significantly antagonized the HCO3- stimulatory action of L-NAME. Furthermore, the increased HCO3- secretion caused by L-NAME was significantly attenuated by prior administration of atropine (1 mg/kg, s.c.) or indomethacin (5 mg/kg, s.c.) and by bilateral vagotomy but was not influenced by sensory deafferentation after capsaicin pretreatment, though none of the treatments had any effect on the changes in blood pressure induced by L-NAME. These results suggest that L-NAME stimulates HCO3- secretion in the gastroduodenal mucosa. This action is associated with the inhibition of NO biosynthesis and may be partly dependent on vagal-cholinergic innervation and mediated by endogenous prostaglandins.
使用一氧化氮（NO）生物合成抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），在麻醉大鼠中研究了NO在胃十二指肠HCO₃⁻分泌调节中的作用。在存在奥美拉唑的情况下，使用pH计法在分腔胃或十二指肠近端测量pH 7.0时的HCO₃⁻分泌。静脉注射L-NAME（1 - 5 mg/kg）以剂量依赖方式增加胃和十二指肠中的HCO₃⁻分泌，同时伴有动脉血压升高。另一种NO合酶抑制剂NG-单甲基-L-精氨酸（50 mg/kg）可模拟L-NAME对HCO₃⁻分泌的刺激作用，但对映体NG-硝基-D-精氨酸甲酯则无此作用，并且同时给予200 mg/kg的L-精氨酸可显著拮抗L-NAME的作用，而D-精氨酸则无此作用。外源性NO供体硝普钠（4 mg/kg）本身可降低HCO₃⁻分泌速率，并显著拮抗L-NAME对HCO₃⁻的刺激作用。此外，预先给予阿托品（1 mg/kg，皮下注射）或吲哚美辛（5 mg/kg，皮下注射）以及双侧迷走神经切断术可显著减弱L-NAME引起的HCO₃⁻分泌增加，而辣椒素预处理后的感觉传入神经切断术则无影响，尽管这些处理均未对L-NAME引起的血压变化产生任何影响。这些结果表明，L-NAME刺激胃十二指肠黏膜中的HCO₃⁻分泌。该作用与NO生物合成的抑制有关，可能部分依赖于迷走胆碱能神经支配，并由内源性前列腺素介导。
