Pulmonary vascular complications during liver cirrhosis can be frequent and severe. A prominent feature of hepatopulmonary syndrome is blunted hypoxic pulmonary vasoconstriction (HPV), illustrating that the acute response to hypoxia is impaired during cirrhosis. The pulmonary response to chronic hypoxia (CH) is unknown. Our purpose was to characterize the pulmonary adaptations to CH in rats with advanced biliary cirrhosis. To investigate this interaction, we induced liver cirrhosis in the rats using common bile duct ligation (CBDL) and exposed them to CH or maintained them in Denver (Den) for 3 weeks. Histologic, biochemical, and hemodynamic responses were evaluated. The response to acute hypoxia, which was assessed by measuring HPV in isolated lungs, was blunted in both the CBDL-Den and CBDL-CH groups. The response to CH was strikingly different. The CBDL-CH rats did not develop pulmonary hypertension compared to the sham-Den rats (mean [± SD] pulmonary artery pressure: sham-Den rats, 19.0 ± 1.2 mm Hg; sham-CH rats, 45.1 ± 2.0 mm Hg; CBDL-CH rats, 23.9 ± 2.1 mm Hg) and showed no evidence of pulmonary arteriole remodeling (Fig 1
) or right ventricular hypertrophy (sham-Den rats, 0.31 ± 0.02 mm Hg; sham-CH rats, 0.59 ± 0.04 mm Hg; CBDL-CH rats, 0.33 ± 0.02 mm Hg).