Candesartan mediates microcirculation in acute necrotizing pancreatitis

Abstract

Aim: In the present study we aimed to determine the effect of an AT-II antagonist candesartan on pancreatic microcirculation in an experimental model of acute necrotizing pancreatitis.

Materials and methods: There were five study groups with 10 animals in each. Pancreatitis was induced by intravenous infusion of cerulein and coadministration of glycodeoxycholate into biliopancreatic canal. Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups, respectively. At 24th and 48th hours; following anaesthesia laparotomy was performed and laser Doppler flowmetry was performed in the pancreatic tissue of the animals. Following scarification blood samples were obtained for amylase, myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the pancreas were obtained for histopathological analysis, endothelial cell apoptosis (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry.

Results: Pancreatic microcirculation was higher in the candesartan treated groups (p < 0.05). Myeloperoxidase, IL-6 and tumour necrosis factor alpha was found to be lower in the candesartan treated groups (p < 0.05). The pancreatic edema and inflammation were found to be reduced in the candesartan treated groups (p < 0.05). Endothelial apoptosis was found to be reduced by cadesartan treatment but it did not reach statistical significance (p > 0.05). Tissue matrix metalloproteinase -9 levels were found to be reduced with candesartan treatment (p < 0.05).

Conclusion: Treatment with candesartan in the early phases of acute necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab. 3, Fig. 6, Ref. 28).

Keywords: acute necrotizing pancreatitis; candesartan; matrix metalloproteinase.; microvascular circulation.