The role of adenosine receptors for pancreatic blood flow in caerulein-induced acute pancreatitis.
PURPOSE: The aim of our study was to evaluate the possible influence of adenosine receptors agonists and antagonists on pancreatic blood flow (PBF) and the development of acute pancreatitis (AP) in rats. MATERIAL AND METHODS: Ninety male Wistar rats were subdivided into ten equal groups, nine rats in each. The study was carried out in two stages. In the first one the first group (control) received i.v. saline infusion for 12 hours. The groups 2-5 (the first stage) received i.v. caerulein infusion as in the first group, but with pretreatment with: in the second group--DPCPX (A1 receptor antagonist), in the third group--CGS 21680 (A2 receptor agonist), in the fourth group--ZM 241385 (A2 receptor antagonist), in the fifth group--IB-MECA (A3 receptor agonist). In the second stage the first group received i.v. caerulein infusion at the dose of 5 micrograms/kg/h for 12 hours. The groups 2-5 (the second stage) received i.v. caerulein infusion as in the first group, but with pretreatment with: in the second group--DPCPX (A1 receptor antagonist), in the third group--CGS 21660 (A2 receptor agonist), in the fourth group--ZM 241385 (A2 receptor antagonist), in the fifth group--IB-MECA (A3 receptor agonist). Pancreatic blood flow was measured by laser Doppler flowmetry. Pancreatic inflammation was evaluated by serum alpha-amylase activity, pancreatic weight and histological changes in the pancreatic tissue. RESULTS: We observed a significant attenuation of serum alpha-amylase activity increase (19.1 +/- 2.8 kIU/L vs 30.12 +/- 2.64 kIU/L), pancreatic weight (expressed as percentage of rat's body weight--0.85 +/- 0.16% vs 1.25 +/- 0.14%), and improvement of PBF (79.8 +/- 6.1% vs 60.1 +/- 3.6%), a reduced degree of pancreatic tissue damage (oedema, leukocyte infiltration, vacuolisation of acinar cells) in the third group (CGS 21680 + caerulein) compared with the first group in the second stage (only caerulein infusion). Neither agonists nor antagonists exerterd any appreciable effects on measured parameters in healthy rats. CONCLUSIONS: Pretreatment with A2 receptors agonist seems to be protective against the damage to the pancreas during the course of caerulein-induced acute pancreatitis in rats. This effect could be due to improvement of pancreatic blood flow. This finding could have some therapeutic implications.