Hori N, Okanoue T, Sawa Y, Itoh Y, Mori T, Takami S, Kashima K
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
J Gastroenterol. 1994 Aug;29(4):460-8. doi: 10.1007/BF02361244.
The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.
作者研究了生长抑素类似物SMS 201-995与低剂量硝酸异山梨酯联合治疗是否能增强这两种药物对硫代乙酰胺诱导的肝硬化大鼠的血流动力学效应。四组肝硬化大鼠分别接受SMS 201-995（0.1微克·分钟-1·千克-1）、硝酸异山梨酯（10微克·分钟-1·千克-1）、两种药物联合或安慰剂治疗。采用放射性微球法对清醒大鼠的血流动力学进行连续测量。SMS 201-995使门静脉血流量减少21±4%，门静脉压力降低17±3%。硝酸异山梨酯通过诱导低压压力反射介导的内脏血管收缩，使门静脉血流量减少20±4%，该药物还使门静脉压力降低14±2%。单独使用硝酸异山梨酯时门静脉阻力升高7.6±3%，联合治疗时门静脉阻力降低18±4%。这种效应可能是由硝酸异山梨酯对静脉血管系统的显著血管舒张作用引起的，因为当该药物与SMS 201-995联合使用时，低剂量硝酸异山梨酯引起的反射性内脏血管收缩消失。联合治疗时门静脉压力的降低更为明显（22±4%），全身血流动力学的变化更为轻微。得出的结论是，SMS 201-995与低剂量硝酸异山梨酯联合治疗可能对肝硬化门静脉高压有益。
