Chen Chien-Ting, Chu Chi-Jen, Lee Fa-Yauh, Chang Full-Young, Wang Sun-Sang, Lin Han-Chieh, Hou Ming-Chih, Wu Shwu-Ling, Chan Che-Chang, Huang Hui-Chun, Lee Shou-Dong
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
Hepatogastroenterology. 2009 Sep-Oct;56(94-95):1261-7.
BACKGROUND/AIMS: The portal hypotensive effect of vasopressin during hemorrhage is less effective than that during stable condition in cirrhotic patients or experimental portal hypertension (the so-called hyposensitivity phenomenon). Recent studies have demonstrated that constitutive nitric oxide activities and bradykinin in hemorrhage-transfused partially portal vein-ligated rats are responsible, at least partly, for the splanchnic hyposensitivity to glypressin (a long acting vasopressin analogue). This study investigated the relative contribution of nitric oxide synthase isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity in rats with cirrhosis induced by common bile duct-ligation (BDL).
Five weeks after BDL, systemic and portal hemodynamics were measured in stable or bleeding BDL rats receiving intravenous infusion of glypressin (0.2 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME, a non-selective nitric oxide synthase inhibitor), L-canavanine (a specific inducible nitric oxide synthase inhibitor) or HOE 140 (a bradykinin B2 receptor antagonist) was administered 45 minutes before the infusion of glypressin. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or various inhibitors.
Splanchnic hyposensitivity to glypressin was demonstrated in the hemorrhage-transfused BDL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding BDL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin.
Constitutive nitric oxide synthase and bradykinin play major roles in the development of splanchnic hyposensitivity to glypressin observed in hemorrhage-transfused rats with biliary cirrhosis.
背景/目的：在肝硬化患者或实验性门静脉高压症中，出血期间血管加压素的门脉降压作用比稳定状态时效果差（即所谓的低敏现象）。最近的研究表明，出血-输血后部分门静脉结扎大鼠体内的组成型一氧化氮活性和缓激肽至少部分导致了内脏对甘氨加压素（一种长效血管加压素类似物）的低敏性。本研究调查了一氧化氮合酶同工型的相对作用以及缓激肽在胆总管结扎（BDL）诱导的肝硬化大鼠内脏低敏性发病机制中的作用。
BDL术后5周，对接受静脉输注甘氨加压素（0.2mg/kg）的稳定或出血的BDL大鼠测量全身和门静脉血流动力学。在治疗组中，在输注甘氨加压素前45分钟给予N（G）-硝基-L-精氨酸甲酯（L-NAME，一种非选择性一氧化氮合酶抑制剂）、L-刀豆氨酸（一种特异性诱导型一氧化氮合酶抑制剂）或HOE 140（一种缓激肽B2受体拮抗剂）。在低血压性出血的大鼠中，抽取4.5ml血液，在给予甘氨加压素或各种抑制剂之前回输50%的抽取血液。
出血-输血后的BDL大鼠表现出对甘氨加压素的内脏低敏性。输注L-NAME可提高出血BDL大鼠的平均动脉压，而不影响门静脉压力。添加L-NAME或HOE 140，但不添加L-刀豆氨酸，可显著且类似地增强甘氨加压素的门脉降压作用。
组成型一氧化氮合酶和缓激肽在出血-输血的胆汁性肝硬化大鼠中观察到的对甘氨加压素的内脏低敏性发展中起主要作用。
