To investigate the effects of low dosage of nitric oxide synthase (NOS) inhibitor Nc-nitro -L-arginine methyl ester ( L-NAME) in two-week treatment on the hyperdynamic circulatory state in rats with cirrhosis. METHODS: Cirrhosis model was induced in male SD rats by injection of 60 % CCL4 oily solution subcutaneously. Cirrhotic rats were treated with L-NAME ( 0.5 mg·kg-1·d-1) by gavage for two weeks. Mean arterial pressure ( AP ), portal pressure(PP), cardiac output ( CO ), cardiac index ( CI ), splanchnic vascular resistance ( SVR ), splanchnic blood flow(SBF) and serum nitrite levels were determined in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-labled microsphere technique and a fluorometric assay, respectively. RESULTS: Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF and nitrite concentration than those of the controls (all,P< 0.01 ). In treated cirrhotic rats, L-NAME significantly attenuated the increase of CO, CI, SBF, nitrite concentration and the decrease of MAP and SVR. In treated cirrhotic rats, L-NAME induced a marked decrease of nitrite concentration than untreated cirrhotic rats[(1.471±0.907)μmol/L vs (4.204±1.253) μmol/L, P<0.01]. CONCLUSION: The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by oral two-week administration of lower dose of L-NAME.%目的:观察小剂量一氧化氮合酶(N0S)抑制剂N-硝基-L-精氨酸甲酯(L-NAME)连续2周治疗对肝硬化大鼠高动力循环状态的影响.方法:用60%四氯化碳油性溶液皮下注射SD大鼠制造肝硬化大鼠模型.对肝硬化大鼠,用L-NAME(0.5mg·kg·d-1)胃管内注入连续治疗2周.用57Co同位素微球技术分别测定L-NAME治疗组、未治疗组及正常对照组的平均动脉压(MAP)、门静脉压(PP)、心输出量(C0)、心脏指数(CI)、内脏血管阻力(SVR)及内脏器官血流量(SBF).用荧光法测定各组大鼠血清亚硝酸盐含量.结果:未治疗组MAP、SVR显著低于正常对照组,而PP、C0、CI、SBF及亚硝酸盐含量则显著高于正常对照组(P值均小于0.01).在治疗组,L-NAME显著缓解了CO、CI、SBF及亚硝酸盐浓度的增加和MAP、SVR的下降.与未治疗组比较,治疗组血清亚硝酸盐浓度明显减少[(1.471±0.907)μmol/Lvs(4.204±1.253)μmol/L,P<0.01].结论:内源性N0在肝硬化血流动力学改变中可能起重要作用.小剂量L-NAME连续2周口服治疗可以缓解肝硬化大鼠的高动力循环状态.
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