Schroeder R A, Ewing C A, Sitzmann J V, Kuo P C
Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
Dig Dis Sci. 2000 Dec;45(12):2405-10. doi: 10.1023/a:1005651327654.
Portal hypertension is associated with a wide range of pulmonary pathophysiologies, ranging from portopulmonary hypertension to hepatopulmonary syndrome. Although the clinical and pathological features of pulmonary dysfunction in this setting have been extensively characterized, the underlying biology is not well understood. Specifically, the role of mediators that regulate mesenteric vascular hemodynamics in portal hypertension, such as nitric oxide and endothelin, have not been studied in the lung. Using a rat model of prehepatic portal hypertension with preserved hepatic function, we examined pulmonary elaboration of endothelial nitric oxide synthase (NOS), inducible NOS, heme oxygenase- 1 (HO-1), heme oxygenase-2 (HO-2), endothelin-1 mRNA, and protein. In comparison to sham controls, portal hypertensive animals exhibited significantly increased pulmonary iNOS and HO-1 mRNA and protein. Cyclic GMP was significantly increased in portal hypertensive lung tissue, suggesting activation of guanylyl cyclase by the endproducts of iNOS and/or HO-1 activity. Using immunohistochemical analysis, iNOS expression was localized to the vascular endothelium, while HO-1 localized to bronchiolar epithelium and macrophages. These results suggest that production of nitric oxide and carbon monoxide may contribute to the pulmonary pathology associated with portal hypertension.
门脉高压与多种肺部病理生理状态相关，从门肺高压到肝肺综合征不等。尽管这种情况下肺功能障碍的临床和病理特征已得到广泛描述，但其潜在生物学机制仍未完全了解。具体而言，调节门脉高压时肠系膜血管血流动力学的介质，如一氧化氮和内皮素，在肺部尚未得到研究。我们使用肝功能保留的肝前性门脉高压大鼠模型，检测了肺组织中内皮型一氧化氮合酶（NOS）、诱导型NOS、血红素加氧酶-1（HO-1）、血红素加氧酶-2（HO-2）、内皮素-1的mRNA和蛋白表达情况。与假手术对照组相比，门脉高压动物的肺组织中诱导型NOS和HO-1的mRNA及蛋白表达显著增加。门脉高压肺组织中的环磷酸鸟苷（cGMP）显著升高，提示诱导型NOS和/或HO-1活性的终产物激活了鸟苷酸环化酶。通过免疫组织化学分析，诱导型NOS表达定位于血管内皮，而HO-1定位于细支气管上皮和巨噬细胞。这些结果表明，一氧化氮和一氧化碳的产生可能导致与门脉高压相关的肺部病理改变。
