1996 Fiscal Year Final Research Report Summary
Role of nitric oxide in the regulation of hepatic microcirculation under surgical stress
| Project/Area Number |
07671416
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | OSAKA CITY UNIVERSITY |
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Principal Investigator |
KUBO Shoji Osaka City University, Medical School, Assistant, 医学部, 助手 (80221224)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masayasu Osaka City University, Medical School, Professor, 医学部, 教授 (80040278)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Nitric Oxide / Nucleotides / Portal pressure / Sinusoidal endotherlial cell / Cytochrome p450 / Glutathione / Hepatic microcirculation |
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| Research Abstract |
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.
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