ROLE OF NITRIC-OXIDE DERIVED FROM ALVEOLAR MACROPHAGES IN THE EARLY PHASE OF ACUTE-PANCREATITIS

Background: Acute pancreatitis is known to be often complicated by lun g injury; however, the pathogenesis of lung injury in the early phase of acute pancreatitis remains unclear, Alveolar macrophages (AMs) have been suggested to contribute to lung injury by releasing various cyto toxic products including nitric oxide (NO), We investigated the role o f AM-derived NO in the pathogenesis of lung injury during the early ph ase of acute pancreatitis. Materials and Methods: Pancreatitis was ind uced in rats by selective pancreatic duct ligation (SPL). The mRNA exp ression of inducible NO synthase (iNOS) in AMs from rats after SPL (at 1, 2, 4, 6, 8, 12, 18, and 24 hr) was examined by reverse-transcripta se polymerase chain reaction method, The in vitro production of NO and superoxide by AMs 24 hr after SPL was measured and the cytotoxic effe ct of AMs on human umbilical vein endothelial cells (HUVECs) was exami ned with or without the NO synthase inhibitor L-N-G-monomethyl-L-argin ine (L-NMMA). The in vivo effect of L-NMMA on lung injury was also exa mined, Results: In this model, serum amylase level peaked 24 hr after SPL, whereas PaO2 bottomed 24 hr after SPL, (In vitro) AMs expressed i NOS mRNA 6 hr after SPL and generated large amounts of NO and superoxi de and demonstrated strong cytotoxicity against HUVECs significantly. This cytotoxicity was reduced by the administration of L-NMMA (ln vivo ) L-NMMA administrated to rats with pancreatitis apparently reduced lu ng edema histologically and improved the PaO2, Conclusion: Our results suggest that, during early phase of acute pancreatitis, AM-derived NO contributes to lung injury. Administration of the NOS inhibitor L-NMM A prevented lung injury in this model. (C) 1996 Academic Press, Inc.