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


METHODS
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.


METHODS
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.
Oruc
Nevin
N
Ege University, Faculty of Medicine, Gastroenterology Department, Bornova, Izmir, Turkey. nevintr@yahoo.com
Ozutemiz
Omer
O
Nart
Deniz
D
Yuce
Gul
G
Celik
Handan A
HA
Ilter
Tankut
T
D000681:Amylases / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D002108:Ceruletide; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009195:Peroxidase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013656:Taurocholic Acid; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D013656:Taurocholic Acid; C070967:L 158809; D002108:Ceruletide; D002216:Captopril; D009195:Peroxidase; D000681:Amylases