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Role of nitric oxide in the regulation of hepatic microcirculation under surgical stress

一氧化氮在手术应激下肝脏微循环调节中的作用

基本信息

批准号：
07671416
负责人：
KUBO Shoji
金额：
$ 1.47万
依托单位：
OSAKA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671416/
关键词：
Nitric Oxide Nucleotides Portal pressure Sinusoidal endotherlial cell Cytochrome p450 Glutathione Hepatic microcirculation チトクロームP450 管微小循環 Nitric oxide

项目摘要

Some nucleotides bind to purine receptors on cultures stellate cells, increase intracellular calcium concentration, enhance the metabolism of inositol phosphate, and induce contraction of these cells. Adenosine, AMP,ADP and ATP induced relaxation of the contraced mesenteric artery. Such relaxation of aorta and mesenteric artery induced by the nucleotides was significantly inhibited by L-nitro-arginine, a NO synthetase minhibitor, indcating the involvement of NO and/or its metabolites in nucleotide-induced relaxation of these arteries. NO was generated by No synthetase in simusoidal endtherial cells. Contraction and relaxation of the constituent cells of porto-sinusoidal walls might be regulated by these ligands in a concerted mechanism.Kinetic analysis showed that administration of lipopolysaccharide (LPS) dose-dependently increased the iNOS and NO generation in the liver. ESR analysis revealed that significant amounts of NO-Hb appeared in the circulating RBC,peaked at 8 hr after LPS administration and decreased thereafter with concominant changes in plasma nitrite and nitrate (No_X). ESR signal responsible for heme-iron nitrosyl complexes was also found in the liver of endotoxemic rats. NO may affect celular metabolism by modulating ferrous enzymes. N^G-iminoethyl-L-ornithine, a potent inhibitor of NOS,inhibited the generation of No, NO-Hb, heme-iron nitrosyl complexes and No_X. Administration of LPS decreased the glutathione levels in plasma and bile, whereas it decreased the hepatic level slightly. N^G-nitro-L-arginene, a NO synthase inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile. These findings showed that NO plays important roles in the pathogenesis of endotoxin shock and multiple organ failure.

一些核苷酸与培养物星状细胞上的嘌呤受体结合，增加细胞内钙浓度，增强磷酸肌醇的代谢，并诱导这些细胞的收缩。腺苷、AMP、ADP和ATP可使收缩的肠系膜动脉舒张。NO合成酶抑制剂L-硝基精氨酸可明显抑制核苷酸对主动脉和肠系膜动脉的舒张作用，提示NO和/或其代谢产物参与了核苷酸对这些动脉的舒张作用。模拟终末细胞NO合成酶产生NO。动力学分析表明，脂多糖（LPS）可剂量依赖性地增加肝内iNOS和NO的生成。ESR分析表明，循环红细胞中出现大量的NO-Hb，在LPS注射后8小时达高峰，此后下降，同时血浆中NO_x和NO_X也发生变化。内毒素血症大鼠肝脏中也发现了血红素-铁亚硝酰复合物的ESR信号。NO可能通过调节亚铁酶而影响细胞代谢。N^G-亚氨乙基-L-鸟氨酸是一种有效的NOS抑制剂，可抑制NO、NO-Hb、血红素-铁-亚硝酰复合物和NO_X的生成。脂多糖可降低血浆和胆汁中谷胱甘肽的含量，而肝脏中谷胱甘肽的含量则略有下降。NO合酶抑制剂N^G-硝基-L-胆甾烯可抑制LPS诱导的血浆和胆汁中谷胱甘肽的降低。提示NO在内毒素休克和多器官功能衰竭的发病机制中起重要作用。