Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis

Background-Capillary leakage with fluid loss into the third space contribut es to many of the early systemic complications in severe acute pancreatitis . There has been increasing interest in endothelin as one of the factors af fecting capillary permeability. Aim-To elucidate further the role of endothelin in the development of capil lary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operate d animals and two models of acute pancreatitis. Methods-Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. Results-Pancreatic and colonic capillary permeability increased stepwise fr om mild to severe acute pancreatitis. Endothelin increased pancreatic and c olonic capillary permeability in healthy animals and animals with mild acut e pancreatitis but had no additional adverse effect in severe acute pancrea titis. Endothelin receptor blockade decreased pancreatic capillary permeabi lity in sham operated rats but had no effect on the colon. In mild and seve re acute pancreatitis, endothelin receptor blockade stabilised increased ca pillary permeability in both the pancreas and colon. Conclusions-Endothelin plays an important role in mediating capillary perme ability in the pancreas. In severe pancreatitis, it increases capillary per meability even outside the pancreas, thereby contributing to capillary leak age. Endothelin receptor blockade significantly reduces capillary permeabil ity in acute pancreatitis both in and outside the pancreas, suggesting a th erapeutic approach to counteract capillary leakage in severe acute pancreat itis.