Localization of inducible nitric oxide synthase in vascular tissue in endotoxic shock

内毒素休克中血管组织中诱导型一氧化氮合酶的定位

• 批准号: 08671765
• 负责人: YAMAMOTO Manabu
• 金额: $ 1.47万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671765/
• 关键词: Nitric oxide synthase; vascular tissue; in situ hybridization; immunohistochemistry

(1)Endotoxic shock was induced by injecting lipopolysaccharide (LPS) intraperitoneally to Wister rats. Aortae from rats treated with LPS for 4 hours showed hyporesponsiveness to phenylephrine. This hyporeactivity was reversed by administration of N^<omega>-Nitro-L-arginine, an inhibitor of nitric oxide synthase.(2)The study using in situ hybridization showed that treatment with LPS for 4h induced expression of inducible nitric oxide synthase (iNOS)mRNA in the aortic wall. The signals for iNOS mRNA were localized in the non-vascular smooth muscle cells (VSMCs) in the tunica adventitia, and not in VSMCs in the tunica media.(3)Immunohisotchemistry study using anti rat iNOS sntibody showed that iNOS-like immunorectivity was identified in the tunica adventitia of aortae from rats treated with LPS.The findings of the present study confirm that LPS administration induces vascular hyporeactivity which is attributable to iNOS induction. The results in in situ hybridization study and immunohisotochemistry study suggest that iNOS induced in the perivascular non-VSMCs is involved in the pathogenesis of endotoxic shock.The study on the heterogeneity in nitric oxide synthase induction in vascular tissues from different organs is now under way in our laboratory.

(1)用内毒素(LPS)诱导Wistar大鼠内毒素休克。经内毒素处理4小时的大鼠主动脉对苯肾上腺素呈低反应。给予一氧化氮合酶抑制剂N^-lt；omega&gt；-Nitro-L-精氨酸可逆转这种低反应性。(2)原位杂交显示，脂多糖处理4h可诱导主动脉壁诱导型一氧化氮合酶(INOSmRNA)的表达。(3)用抗大鼠iNOS抗体进行免疫组化研究表明，LPS处理的大鼠主动脉外膜有iNOS样免疫反应性。原位杂交和免疫组织化学研究结果提示，血管周围非VSMCs诱导的iNOS参与了内毒素休克的发病过程。本实验室正在对不同器官血管组织中诱导型一氧化氮合酶的异质性进行研究。

项目成果

Iranami H,Hatano Y,Tsukiyama Y,Yamamoto M,Maeda H,Mizumoto K: "Halothane inhibition of acetylcholine-induced relaxation in rat mesentereic arteri and aorta." Can J Anaesth. 44. 1196-1203 (1997)

Iranami H、Hatano Y、Tsukiyama Y、Yamamoto M、Maeda H、Mizumoto K：“氟烷抑制乙酰胆碱诱导的大鼠肠系膜动脉和主动脉松弛。”

Yamamoto M, Hatano Y.et al.: "Different effects of hulothane,isoflurane and sevoflurane on sarcoplusmin reticalum of vascular smooth muscle in dog mesenteric artery" Acta Anaesth Scand. 41. 376-380 (1997)

Yamamoto M，Hatano Y.et al.：“hulothane、异氟烷和七氟烷对狗肠系膜动脉血管平滑肌肌蛋白网的不同影响”Acta Anaesth Scand。

Iranami H, Hatano Y, et al.: "A beta-adrenoreceptor agonist evokes a nitric oxide-cGMP relaxation mechanism modulated by adenylate cyclase in rat aorta" Anesthesiology. 85. 1129-1138 (1996)

Iranami H、Hatano Y 等人：“β-肾上腺素受体激动剂在大鼠主动脉中引起由腺苷酸环化酶调节的一氧化氮-cGMP 松弛机制”麻醉学。

Ogawa K,Yamamoto M,Mizumoto K,Hatano Y.: "Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries." Can J Anaesth. 44. 426-432 (1997)

Okawa K、Yamamoto M、Mizumoto K、Hatano Y.：“挥发性麻醉剂可减轻离体狗脑动脉中低碳酸血症引起的收缩。”

Ogawa K, Yamamoto M et al.: "Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral artery" Can J Anaesth. 44. 426-432 (1997)

Okawa K、Yamamoto M 等人：“挥发性麻醉剂可减轻离体狗脑动脉中低碳酸血症引起的收缩”Can J Anaesth。