UNLABELLED
Biliary regurgitation plays important role in gastro-esophageal reflux disease and postoperative complications. Our major aims were to find out the consequences of short-term exposure with luminal bile on mucosal microcirculation and nitric oxide synthesis, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition. The experiments were performed on inbred mongrel dogs. Group 1 (n=5) served as a saline-treated control, while in group 2 (n=5) the esophagus was exposed to bile for 3 h. In group 3 (n=5) the animals were pre-treated with 7-nitroindazole (7-NI), to inhibit the neuronal isoform of nitric oxide synthase. In group 4 (n=5) phosphatidylcholine (PC) solution (50 mg/kg) was administered iv before the biliary challenge. The microcirculation of the mucosa was observed by intravital videomicroscopy; myeloperoxidase and nitric oxide synthase activities, the degree of mast cell degranulation and tissue damage were evaluated via tissue biopsies. Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation, and the red blood cell velocity (VRBC) and the diameter of the postcapillary venules (VD) increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared with the control values. 7-NI treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. In contrast, PC pretreatment reversed the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity increases, and the mast cell degranulation.
CONCLUSIONS
The neuronal nitric oxide synthase--mast cell axis plays an important role in the esophageal mucosal defense system. Systemic PC pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.