The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome
The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome
复制标题
DOI：
10.1053/gast.1997.v113.pm9247483
复制
发表时间：
1997-08-01
期刊：
影响因子：
29.4
通讯作者：
Ku, DD
中科院分区：
文献类型：
--
作者：
Fallon, MB;Abrams, GA;Ku, DD
背景和目标：肝硬化综合征是指肝脏疾病时肺内血管扩张导致动脉气体交换受损，其发病机制尚不清楚，但可能与一氧化氮有关。大鼠胆总管结扎是肝硬化综合征的一种模型，但尚无研究评价NO在该模型肺血管扩张中的作用。本研究的目的是确定NO是否参与胆管结扎后肺内血管舒张。方法：胆管结扎后测定肺动脉环内皮和诱导型NO合酶（NOS）水平和定位以及NO活性。胆管结扎后肺内皮细胞NOS水平升高，肺泡血管染色增强，肺诱导型NOS水平或定位没有变化，增加内皮NOS水平与气体交换的改变，并伴随着增强NO活性和钝化反应苯肾上腺素，可逆的NOS抑制，在肺动脉环。门静脉结扎的动物，不发展肺内血管舒张，肺NOS的生产或在肺动脉环NO活性没有变化。结论：NO来源于肺血管内皮细胞NOS，参与了动物肝硬化综合征肺内血管扩张。
Background & Aims: The hepatopulmonary syndrome occurs when intrapulmonary vasodilatation causes impaired arterial gas exchange in liver disease, The pathogenesis is poorly understood, although nitric oxide may be involved, Common bile duct ligation in the rat is a model of the hepatopulmonary syndrome, but no studies have evaluated NO in pulmonary vasodilatation in this model. The aim of this study was to determine whether NO contributes to intrapulmonary vasodilatation after bile duct ligation, Methods: Endothelial and inducible NO synthase (NOS) levels and localization and NO activity in pulmonary artery rings were assessed after bile duct ligation, Results: Pulmonary endothelial NOS levels increased and alveolar vascular staining was enhanced after bile duct ligation, No change in pulmonary inducible NOS levels or localization was detected, Increased endothelial NOS levels correlated with alterations in gas exchange and were accompanied by enhanced NO activity and a blunted response to phenylephrine, reversible by NOS inhibition, in pulmonary artery rings. Portal-vein-ligated animals, which do not develop intrapulmonary vasodilatation, had no changes in pulmonary NOS production or in NO activity in pulmonary artery rings. Conclusions: NO, derived from pulmonary vascular endothelial NOS, contributes to intrapulmonary vasodilatation in animal hepatopulmonary syndrome.