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 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.

• Authors: Nevin Oruc, Omer Ozutemiz, Deniz Nart, Gul Yuce, Handan A Celik, Tankut Ilter
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 62 Issue 4 Pg. 353-60 (Jul 2010) ISSN: 1618-1433 [Electronic] Germany
• PMID: 19525099 (Publication Type: Journal Article)

Chemical References

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

Topics

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