NITRIC-OXIDE IN PANCREATIC-SECRETION AND HORMONE-INDUCED PANCREATITISIN RATS

The aim of the present study was to determine the role of endogenous n itric oxide (NO) in pancreatic secretion in vivo and amylase release f rom pancreatic acini in vitro and in caerulein-induced acute pancreati tis in rats. Blockade of NO synthase by N-G-nitro-L-arginine (L-NNA) ( 2.5 mg/kg iv) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 mu g/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. Th is inhibitory effect was partially reversed when L-arginine (50 mg/kg- h iv) was added to L-NNA. L-Arginine alone (50 mg/kg iv) did not affec t basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (cae rulein or urecholine) stimulated amylase release. Infusion of caerulei n (5 mu g/kg-h) for 5 h produced histological changes of acute edemato us pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA done also reduced the pancreatic blood flow and caused a significant increase i n pancreatic weight and protein content. L-NNA significantly potentiat ed the inflammatory changes in the pancreas caused by caerulein. Addit ion of L-arginine enhanced the pancreatic blood flow and ameliorated t he pancreatitis induced by caerulein alone or that combined with L-NNA . We conclude that NO is involved in the stimulation of pancreatic sec retion in vivo and exhibits a beneficial effect on pancreatitis, proba bly by improving the pancreatic blood flow.