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

一些核苷酸与培养的星状细胞上的嘌呤受体结合，增加细胞内钙浓度，增强肌醇磷酸的代谢，并诱导这些细胞收缩。腺苷、AMP、ADP和ATP诱导收缩的肠系膜动脉松弛。这种由核苷酸引起的主动脉和肠系膜动脉的松弛被一氧化氮合成酶抑制剂l -硝基精氨酸显著抑制，表明一氧化氮和/或其代谢物参与了核苷酸引起的这些动脉的松弛。一氧化氮是由一氧化氮合成酶产生的。这些配体可能以协调一致的机制调节门窦壁组成细胞的收缩和松弛。动力学分析表明，脂多糖（LPS）剂量依赖性地增加了肝脏中iNOS和NO的生成。ESR分析显示，循环红细胞中出现了大量的NO-Hb，在LPS给药后8小时达到峰值，随后随着血浆亚硝酸盐和硝酸盐（No_X）的变化而下降。在内毒素中毒大鼠肝脏中也发现了血红素-亚硝基铁复合物的ESR信号。NO可能通过调节铁酶影响细胞代谢。N^ g -亚氨基乙基- l-鸟氨酸是一种有效的NOS抑制剂，可抑制No、No - hb、血红素-铁亚硝基配合物和No_X的生成。LPS可降低血浆和胆汁中的谷胱甘肽水平，而肝脏中的谷胱甘肽水平略有下降。一氧化氮合酶抑制剂N^ g -硝基- l -精氨酸可抑制lps诱导的血浆和胆汁中谷胱甘肽的减少。这些结果表明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。

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.