Nitric oxide induction in a rat model of selective pancreatic ischemia and reperfusion
Viola, G.; al-Mufti, R.A.; Sohail, M.; Williamson, R.C.; Mathie, R.T.
Hepato-Gastroenterology 47(35): 1250-1255
2000
ISSN/ISBN: 0172-6390 PMID: 11100325 Document Number: 520187
Background/Aims: 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 pancreas and lung. Methodology: Pancreatic ischemia was achieved by occlusion of the 4 main pancreatic arteries for 40min; 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 pancreas and lung was higher than in shams (median: 0.73 vs. 0.54pmol/mg protein/min in the pancreas (P=0.0082); 1.38 vs. 0.68pmol/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 131.6mumol/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.