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

（1）用内毒素（LPS）诱导Wister大鼠内毒素休克。LPS处理4小时的大鼠主动脉对苯肾上腺素呈低反应性。这种低反应性可通过给予<omega>一氧化氮合酶抑制剂N^ -硝基-L-精氨酸逆转。（2）原位杂交结果显示，LPS处理4 h可诱导主动脉壁诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）mRNA表达。iNOSmRNA的信号定位于图尼卡外膜的非血管平滑肌细胞（VSMCs），而不在图尼卡中膜的VSMCs中。（3）免疫组化结果显示，LPS诱导的大鼠肠系膜外膜图尼卡出现iNOS样免疫反应性，证实LPS诱导的血管低反应性与iNOS的诱导有关。原位杂交和免疫组织化学研究结果表明，血管周围非VSMCs诱导的iNOS参与了内毒素休克的发病过程。

(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.