Nitric oxide induction in a rat model of selective pancreatic ischemia and reperfusion.
OBJECTIVE
Ischemia and reperfusion of the pancreas may be important in aggravating the course of acute pancreatitis. In a rat model of selective pancreatic ischemia and reperfusion, we studied plasma levels of nitric oxide and expression of nitric oxide synthase in the pancrease and lung.


METHODS
Pancreatic ischemia was achieved by occlusion of the 4 main pancreatic arteries for 40 min; this was followed by a 7-hour reperfusion period (group A, 10 rats). Outcome measures were compared with those of animals undergoing a sham operation (group B, 10 rats).


RESULTS
Pancreatic damage in group A animals was demonstrated by increased serum alpha-amylase and by macroscopic and microscopic evidence. Total nitric oxide synthase activity in pancrease and lung was higher than in shams [median: 0.73 vs. 0.54 pmol/mg protein/min in the pancreas (P = 0.0082); 1.38 vs. 0.68 pmol/mg protein/min in the lung (P = 0.023)]; this was mainly due to activation of the inducible isoform of the enzyme. There was an associated 58.2% increase in plasma levels of nitric oxide metabolites [from mean 55.0 to 131.6 mumol/L (P < 0.001)]. Immunohistochemistry confirmed expression of inducible nitric oxide synthase and nitric oxide-mediated oxidative damage (nitrotyrosine) in both pancreas and lung.


CONCLUSIONS
Ischemia and reperfusion of the pancreas induces pancreatic damage, overexpression of inducible nitric oxide synthase and oxidative damage within the pancreas and lung.
Viola
G
G
Department of Gastrointestinal Surgery, Imperial College School of Medicine, Hammersmith Hospital, London, England.
al-Mufti
R A
RA
Sohail
M
M
Williamson
R C
RC
Mathie
R T
RT
D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010179:Pancreas / Q000098:blood supply* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D000516:alpha-Amylases / Q000097:blood
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000516:alpha-Amylases