Expression of Inducible Nitric Oxide Synthase (iNOS) in the Epithelial Cells of the Distended Bile Duct by the Bile Ductal Ligation

ABSTRACT

PURPOSE: Recent studies in an obstructive jaundice rat model showed that the bile duct epithelium is also very important in the bile duct dilatation besides the increased luminal pressure. This study evaluated the role of iNOS in the bile duct epithelium in a rat obstructive jaundice model. METHODS: Bile duct ligations were performed in male Sprague-Dawley rats. The bile ducts were harvested on seven consecutive days. Immunohistochemical staining in the bile duct was performed using anti-iNOS polyclonal antibodies. Aminoguanidine (an iNOS antagonist) was injected intraperitoneally after bile duct ligation (0, 100, and 200 mg/kg/day, n=6 in each group). One week after surgery, the diameter of bile duct was measured and bile was collected for NO analysis by 280NOA (Silvers). RESULTS: The iNOS expression level was increased in the dilated ductal epithelium after the bile duct ligation but not in the normal epithelium. Aminoguanidine decreased the mean diameter of the bile duct after the bile duct ligation 11/-2.3 mm in the duct ligation only group; 7.5+/-0.75 mm in the 100 mg/kg/day aminoguanidine; 6+/-0.82 mm in the 200 mg/kg/day of aminoguanidine group (mean+/-SE, P<0.05). The NO concentration in the bile was decreased by aminoguanidine 16+/-4.2 mM in the sham operation group; 40+/-4.5 mM in duct ligation only group; 34+/-6.4 mM in the 100 mg/kg/day of aminoguanidine group; 11+/-1.2 mM in the 200 mg/kg/day of aminoguanidine group (mean+/-SE). CONCLUSION: Bile duct ligation induced iNOS expression in the dilated bile duct epithelium and the iNOS antagonist partially inhibited bile duct dilatation. iNOS induction in the epithelium is partly responsible for the dilatation of the bile duct after duct ligation.