EFFECT OF KININ INHIBITION IN EXPERIMENTAL ACUTE-PANCREATITIS

Activation of the endogenous kinin system is a consistent observation in acute pancreatitis and has repeatedly been implicated in the pathop hysiology of the disease. We have studied the effect of a potent brady kinin antagonist on the onset and development of acute pancreatitis in four unrelated animal models. Pancreatitis was induced in rats by eit her supramaximal stimulation with caerulein, intraductal injection of sodium taurocholate, or pancreatic duct ligation with secretin infusio n, and in mice by feeding a choline-deficient, ethionine-supplemented diet. The potent, long-acting bradykinin antagonist HOE-140 was admini stered subcutaneously (0.1 mg/kg every 5 h). Effective kinin inhibitio n had no effect on pancreatitis-associated mortality, the extent of mo rphological damage and inflammation, or the intracellular distribution of lysosomal hydrolases. Pancreatic edema was only reduced in caerule in-induced pancreatitis, the only model in which edema formation was p aralleled by increased vascular permeability. We conclude that, contra ry to previous suggestions, kinins do not play a predominant role in t he development of acute pancreatitis. Their participation is strictly limited to vascular events and does not involve the early cell biologi cal alterations in pancreatic acinar cells.