Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: A new therapeutic target?

WOS: 000280425200003PubMed ID: 19525099Objective: Pancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type 1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis. Design: Rats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20 mu g/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct. Interventions: Captopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed. Results: Captopril decreased serum amylase (10,809 +/- 1867 vs. 4085 +/- 1028 U/L, p<0.01), myeloperoxidase activity (3.5 +/- 0.5 vs. 1.5 +/- 0.1, p<0.05) and histopathological score (5.0 +/- 0.4 vs. 1.1 +/- 0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1 +/- 1.2 vs. 3.4 +/- 0.5, p<0.01), pancreatic parenchymal necrosis (4.5 +/- 0.6 vs. 0.0 +/- 0.0, p<0.001), fatty necrosis (2.8 +/- 0.9 vs. 0.1 +/- 0.1, p<0.01) and edema (2.1 +/- 0.3 vs. 1.4 +/- 0.3, p