Acute pancreatitis is an inflammatory disease characterized by pancreatic tissue
edema, acinar cell
necrosis,
hemorrhage and
inflammation of the damaged gland. It is believed that acinar cell injury is initiated by the activation of digestive
zymogens inside the acinar cells, leading finally to the autodigestion of the pancreas. Previous study in our laboratory demonstrated that
cerulein-induced
acute pancreatitis was associated with an up-regulation of local renin-angiotensin system (RAS) in rat pancreas. Therefore, the utilization of RAS inhibitors may provide a novel and alternative treatment for
acute pancreatitis. By means of a rat model of
cerulein-induced
acute pancreatitis, results from the present study showed that an
intravenous injection of
saralasin, an antagonist for
angiotensin II receptors, at a dose of 40 microg/kg 30 min before the induction of
acute pancreatitis significantly attenuated pancreatic
edema. Results from the biochemical measurements showed that pretreatment with
saralasin at a dose of 20 microg/kg markedly reduced pancreatic injury, as evidenced by the decreased activities of
alpha-amylase and
lipase in plasma. However, the same recipe of
ramiprilat, a specific inhibitor for
angiotensin-converting enzyme, at a dose of 20 microg/kg did not provide any protective effect against
acute pancreatitis. On the contrary, pretreatment with
ramiprilat at a dose 40 microg/kg enhanced
cerulein-induced pancreatic injury. Results from histopathological analysis of these RAS inhibitors further confirmed with those results as obtained from biochemical analysis. These data indicate that administration of
saralasin but not
ramiprilat could be protective against
acute pancreatitis and that activation of pancreatic RAS in
acute pancreatitis may play a role in pancreatic tissue injury.