| Co-Investigator(Kenkyū-buntansha) |
OSAKA Kazuhiro The Jikei University School of Medicine, Assistant, 医学部, 助手
TSUCHIYA Takumi The Jikei University School of Medicine, Assistant, 医学部, 助手 (80207406)
HARADA Makoto The Jikei University School of Medicine, Assistant, 医学部, 助手
MURAKAMI Shigeto The Jikei University School of Medicine, Assistant, 医学部, 助手 (20219893)
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| Research Abstract |
Because renin and angiotensin levels are increased in patients with liver eirrhosis, it could be logical to investigate the effects of angiotensin converting enzyme(ACE)inhibitors on portal hemodynamics. Additionaly, given the evidences that some prostaglandin(PG)may be involved in regulation of hepatic resistance and perhaps even in maintenance of the hyperdynamic state, more studies of PG effects on hepatic and portal hemodynamics are warranted.
Because of few studies investigated the above these issues, we started to investigate the renin, angiotensin II, catecholamines, and prostanoids levels both in systemic (S) and portal (P) blood circulations from animal models and the patients with liver cirrhosis. In two experimetal animal models (the rats with CCl_4-induced liver cirrhosis (LC rat) and the rats with portal hypertension induced by 2 weeks partial ligation (PH rat)) and control (C) rats, we measured the stable PG metabolites 6-keto-prostagiandin F_<1alpha> (6KPG), from PGI_2, a
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nd thromboxane B_2 (TXB_2), from TXA_2 by radioimmunoassay employing rabbit-antibody. The 6KPG concentrations in tge S and P circulations were approximately 2 and 5 times higher (p<0.05) in LC rats(S, 2008 <plus-minus>549 pg/ml ; P, 4802<plus-minus>654 pg/ml) than in C rats (S, 1116<plus-minus>186 pg/ml ; P 983<plus-minus>177 pg/ml (mean<plus-minus>SE)). The tissue 6KPG of the portal vein was significantly higher in LC and PH rats than in C rats (255<plus-minus>36, 415<plus-minus>43, 142<plus-minus>23 pg/mgWW, respectively). The S and P TXB_2 concentrations were higher in LC rats(S, 3059<plus-minus>1309 pg/ml ; P, 2315<plus-minus>633 pg/ml) than in PH-rats (S, 1243(]SY.+-. (]178 pg/ml ; P, not obtained) and C rats (S, 343(]SY.+-.[)63 pg/ml ; P, 417(]SY.+-.[)65 pg/ml). The tissue TXB_2 levels did not differ between the model rats and the C rats. In the clinical study, we collected the PG's blood samples from 11 cirrhotic patients. 6KPG and TXB_2 levels in the P circulation were significantly (p<0.01) higher than (10 and 14 times) those in the S circulation : 57(]SY.+-.[)31 and 484(]SY.+-.[)192 pg/ml in P, 4(]SY.+-.[)1 and 50(]SY.+-.[)8 pg/ml in S, respectively. These results indicated that production of PG, particularly PGI_2, is stimulated in the portal circulation in liver cirrhosis and could be involved in the elevation of intraportal pressure.
In the second step, we investigated the renal effects of an ACE inhibitor, enalapril in ten patients with liver cirrhosis. Enalapril was administered orally at the dose of 10 mg for eight days. As a result we observed clinically favorable renal effects of enalapril, that is, it increased creatinine clearance markedly and produced considerable natriuresis. This results suggested that enalapril, a ACE inhibitor, may be one of tools for the treatment of cirrhotic condition complicated with peripheral edema and ascites. Less
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