Martínez-Cuesta M A, Barrachina M D, Beltrán B, Calatayud S, Esplugues J
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
J Pharm Pharmacol. 1997 Oct;49(10):988-90. doi: 10.1111/j.2042-7158.1997.tb06029.x.
Because of the evidence that endogenous nitric oxide (NO) plays an essential role in the physiological regulation of gastrointestinal motility we have investigated, by use of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), the role of endogenous NO in the acute endotoxin-induced changes of gastrointestinal transit. Pre-treatment with E. coli endotoxin (100 micrograms kg-1, i.v.) induced a significant increase in the gastrointestinal transit of a charcoal suspension in anaesthetized rats. Previous administration of the NO synthase inhibitor, L-NAME (10 mg kg-1, i.v.) significantly prevented the effects of endotoxin. L-arginine (200 mg kg-1, i.v.) and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P (SPA), significantly reversed the effects of L-NAME on gastrointestinal transit in rats treated with endotoxin. Pre-treatment with dexamethasone (5 mg kg-1, s.c., twice), an inhibitor of the expression of inducible NO synthase, did not affect the increase in the gastrointestinal transit through constitutive NO synthesis. The results suggest that constitutive nitric oxide is involved in the increase of gastrointestinal transit induced by endotoxin and that the reduction in transit induced by L-NAME in endotoxin-treated rats is mediated by endogenous tachykinins.
由于有证据表明内源性一氧化氮（NO）在胃肠动力的生理调节中起重要作用，我们使用NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），研究了内源性NO在急性内毒素诱导的胃肠转运变化中的作用。用大肠杆菌内毒素（100微克/千克，静脉注射）预处理可使麻醉大鼠木炭悬液的胃肠转运显著增加。预先给予NO合酶抑制剂L-NAME（10毫克/千克，静脉注射）可显著预防内毒素的作用。L-精氨酸（200毫克/千克，静脉注射）和P物质拮抗剂[D-脯氨酸2，D-色氨酸7，9]-P物质（SPA）可显著逆转L-NAME对内毒素处理大鼠胃肠转运的影响。用地塞米松（5毫克/千克，皮下注射，两次）预处理，一种诱导型NO合酶表达抑制剂，并不影响通过组成型NO合成引起的胃肠转运增加。结果表明，组成型一氧化氮参与了内毒素诱导的胃肠转运增加，并且内毒素处理大鼠中L-NAME诱导的转运减少是由内源性速激肽介导的。
