Pulmonary expression of iNOS and HO-1 protein is upregulated in a rat model of prehepatic portal hypertension

Portal hypertension is associated with a wide range of pulmonary pathophysi ologies, ranging from portopulmonary hypertension to hepatopulmonary syndro me. Although the clinical and pathological features of pulmonary dysfunctio n in this setting have been extensively characterized, the underlying biolo gy is not well understood. Specifically, the role of mediators that regulat e mesenteric vascular hemodynamics in portal hypertension, such as nitric o xide and endothelin, have not been studied in the lung. Using a rat model o f prehepatic portal hypertension with preserved hepatic function, we examin ed pulmonary elaboration of endothelial nitric oxide synthase (NOS), induci ble NOS, heme oxygenase-1 (HO-1), heme oxygenase-2 (HO-2), endothelin-1 mRN A, 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 l ocalized to the vascular endothelium, while HO-1 localized to bronchiolar e pithelium and macrophages. These results suggest that production of nitric oxide and carbon monoxide may contribute to the pulmonary pathology associa ted with portal hypertension.