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

Abstract

Objective 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 type1 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 μg/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<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration. Conclusions This study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.