Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation

Background/Aims: Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS. Methods: Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with 141Ce-labeled microspheres (15-μm diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO2 was studied using L-NAME. Results: A decrease of PaO2 below 82.7 mmHg (the mean value−2σ in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO2 was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO2 in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO2. Conclusions: These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.