Increased nitric oxide activity in a rat model of acute pancreatitis

Abstract

Background—Overproduction of nitric oxide (NO) via induction of the inducible NO synthase (iNOS) is an important factor in the haemodynamic disturbances of several inflammatory states.Aims—To identify the role of NO in a caerulein induced model of acute pancreatitis in the rat.Methods—Arterial blood pressure and plasma NO metabolites were measured at zero and seven hours in adult male Wistar rats administered caerulein (n=10) or saline (n=10). Pancreatic activity of NOS (inducible and constitutive) was assayed biochemically. The pancreatic expression and cellular localisation of NOS and nitrotyrosine (a marker of peroxynitrite induced oxidative tissue damage) were characterised immunohistochemically.Results—Compared with controls at seven hours, the pancreatitis group displayed raised plasma NO metabolites (mean (SEM) 70.2 (5.9) versus 22.7 (2.2) μmol/l, pConclusions—In this experimental model of acute pancreatitis, iNOS induction and oxidative tissue damage in the pancreas is associated with raised systemic NO and arterial hypotension. Excess production of NO arising from the inducible NO synthase may be an important factor in the systemic and local haemodynamic disturbances associated with acute pancreatitis.