Inhibition of Renin-Angiotensin System in Experimental Acute Pancreatitis in Rats: A New Therapeutic Target?

Exp Toxicol Pathol. 2010 Jul;62(4):353-60. doi: 10.1016/j.etp.2009.05.001. Epub 2009 Jun 13.

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 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 20microg/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+/-1028U/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.

MeSH terms

  • Amylases / blood
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Captopril / administration & dosage
  • Captopril / therapeutic use*
  • Ceruletide
  • Disease Models, Animal
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use*
  • Injections, Intraperitoneal
  • Male
  • Neutrophil Infiltration / drug effects
  • Pancreas / drug effects
  • Pancreas / enzymology
  • Pancreas / pathology
  • Pancreatitis, Acute Necrotizing / blood
  • Pancreatitis, Acute Necrotizing / drug therapy*
  • Pancreatitis, Acute Necrotizing / enzymology
  • Pancreatitis, Acute Necrotizing / physiopathology
  • Peroxidase / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / drug effects*
  • Taurocholic Acid
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Imidazoles
  • Tetrazoles
  • Taurocholic Acid
  • L 158809
  • Ceruletide
  • Captopril
  • Peroxidase
  • Amylases