Miura M, Ichinose M, Kageyama N, Tomaki M, Takahashi T, Ishikawa J, Ohuchi Y, Oyake T, Endoh N, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Allergy Clin Immunol. 1996 Jul;98(1):144-51. doi: 10.1016/s0091-6749(96)70236-1.
To examine the role of endogenous nitric oxide in allergic airway inflammation, we investigated the effect of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (l-NAME), on antigen-induced airway microvascular leakage in actively sensitized guinea pigs by using Evans blue dye. Three weeks after sensitization with ovalbumin (10 micrograms), the tracheas were cannulated, and lungs were artificially ventilated. Animals were pretreated with atropine and propranolol (both 1 mg/kg, intravenously) to avoid neural modification. Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg). This inhibition by L-NAME was significantly reversed by co-administration of L-arginine (100 mg/kg, intravenously). Pretreatment with a vasoconstrictor, phenylephrine (20 micrograms/kg, intravenously), had no inhibitory effects on antigen-induced airway microvascular leakage despite increasing systemic blood pressure. Inhalation of representative mast cell-derived mediators, histamine (2 mg/ml, 1 minute) or leukotriene D4 (5 micrograms/ml, 1 minute), produced significant microvascular leakage in all airways. L-NAME (10 mg/kg, intravenously) partially but significantly inhibited leukotriene D4-induced leakage, whereas histamine-induced leakage was not affected. These results suggest that endogenous nitric oxide acts to increase airway microvascular leakage after airway allergic reaction.
为研究内源性一氧化氮在过敏性气道炎症中的作用，我们通过伊文思蓝染料，研究了一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）对主动致敏豚鼠抗原诱导的气道微血管渗漏的影响。用卵清蛋白（10微克）致敏三周后，将气管插管，对肺进行人工通气。动物预先用阿托品和普萘洛尔（均为1毫克/千克，静脉注射）处理以避免神经调节。吸入卵清蛋白（3毫克/毫升，1分钟）激发在所有气道部分均引起显著的微血管渗漏，静脉注射L-NAME（1和10毫克/千克）预处理可剂量依赖性地显著抑制该渗漏，而无活性对映体D-NAME（10毫克/千克）则无此作用。L-NAME的这种抑制作用可通过静脉注射L-精氨酸（100毫克/千克）共同给药而显著逆转。预先用血管收缩剂去氧肾上腺素（20微克/千克，静脉注射）处理，尽管可升高全身血压，但对抗原诱导的气道微血管渗漏无抑制作用。吸入代表性的肥大细胞衍生介质组胺（2毫克/毫升，1分钟）或白三烯D4（5微克/毫升，1分钟），在所有气道均产生显著的微血管渗漏。L-NAME（10毫克/千克，静脉注射）部分但显著地抑制白三烯D4诱导的渗漏，而组胺诱导的渗漏则不受影响。这些结果表明，内源性一氧化氮在气道过敏反应后可增加气道微血管渗漏。
