Zhang Zong-Qi, Shi Bin, Wu Guo-Qiang, Qin Kai-Rong, Jiang Zong-Lai, Zhu Liang
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Eur J Pharmacol. 2009 Jun 24;613(1-3):108-13. doi: 10.1016/j.ejphar.2009.04.039. Epub 2009 May 3.
Portal hypertension is a hemodynamic syndrome due to pathological increase in portal flow and portal pressure. These pathological changes in external flow loads will inevitably cause vascular remodeling in the portal vein, which is usually measured by an opening angle. The present study showed that carbon tetrachloride (CCl(4))-induced portal hypertension fully developed at 8 weeks and the opening angle of portal vein increased progressively in the pathogenesis of intrahepatic portal hypertension which was significantly augmented at 10 weeks. Although portal pressure and portal flow were reduced, treatment with either propranolol or nifedipine alone for 3 weeks did not decrease the augmented opening angle of the portal vein, while combined treatment with propranolol and nifedipine markedly reduced the increased opening angle of the portal vein and endothelial nitric oxide synthase (eNOS) mRNA expression but not inducible nitric oxide synthase (iNOS) mRNA expression. The decreasing effect of propranolol plus nifedipine on the elevated opening angle was significantly weakened by L-arginine and markedly reinforced by N-nitro-l-arginine-mythel-ester (L-NAME). These results indicate that combined use of propranolol and nifedipine ameliorates portal vein remodeling in portal hypertension at least by the nitric oxide-dependent way.
门静脉高压是一种由于门静脉血流和门静脉压力病理性增加所致的血流动力学综合征。这些外部血流负荷的病理变化将不可避免地导致门静脉血管重塑，通常通过开放角来衡量。本研究表明，四氯化碳（CCl₄）诱导的门静脉高压在8周时完全形成，在肝内门静脉高压发病机制中门静脉开放角逐渐增加，在10周时显著增大。尽管门静脉压力和门静脉血流减少，但单独使用普萘洛尔或硝苯地平治疗3周并未降低增大的门静脉开放角，而普萘洛尔和硝苯地平联合治疗显著降低了门静脉增大的开放角以及内皮型一氧化氮合酶（eNOS）mRNA表达，但对诱导型一氧化氮合酶（iNOS）mRNA表达无影响。L-精氨酸显著削弱了普萘洛尔加硝苯地平对升高的开放角的降低作用，而N-硝基-L-精氨酸甲酯（L-NAME）则显著增强了该作用。这些结果表明，普萘洛尔和硝苯地平联合使用至少通过一氧化氮依赖途径改善门静脉高压中的门静脉重塑。
