THE ROLE OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE IN THE PATHOGENESIS OF A RAT MODEL OF HEPATOPULMONARY SYNDROME

Background & Aims: The hepatopulmonary syndrome occurs when intrapulmo nary vasodilatation causes impaired arterial gas exchange in liver dis ease, The pathogenesis is poorly understood, although nitric oxide may be involved, Common bile duct ligation in the rat is a model of the h epatopulmonary 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 duc t ligation, Methods: Endothelial and inducible NO synthase (NOS) level s and localization and NO activity in pulmonary artery rings were asse ssed after bile duct ligation, Results: Pulmonary endothelial NOS leve ls increased and alveolar vascular staining was enhanced after bile du ct ligation, No change in pulmonary inducible NOS levels or localizati on was detected, Increased endothelial NOS levels correlated with alte rations in gas exchange and were accompanied by enhanced NO activity a nd a blunted response to phenylephrine, reversible by NOS inhibition, in pulmonary artery rings. Portal-vein-ligated animals, which do not d evelop intrapulmonary vasodilatation, had no changes in pulmonary NOS production or in NO activity in pulmonary artery rings. Conclusions: N O, derived from pulmonary vascular endothelial NOS, contributes to int rapulmonary vasodilatation in animal hepatopulmonary syndrome.