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 pathophysiology of the disease. We have studied the effect of a potent bradykinin antagonist on the onset and development of acute pancreatitis in four unrelated animal models. Pancreatitis was induced in rats by either supramaximal stimulation with caerulein, intraductal injection of sodium taurocholate, or pancreatic duct ligation with secretin infusion, and in mice by feeding a choline-deficient, ethionine-supplemented diet. The potent, long-acting bradykinin antagonist HOE-140 was administered subcutaneously (0.1 mg/kg every 5 h). Effective kinin inhibition had no effect on pancreatitis-associated mortality, the extent of morphological damage and inflammation, or the intracellular distribution of lysosomal hydrolases. Pancreatic edema was only reduced in caerulein-induced pancreatitis, the only model in which edema formation was paralleled by increased vascular permeability. We conclude that, contrary to previous suggestions, kinins do not play a predominant role in the development of acute pancreatitis. Their participation is strictly limited to vascular events and does not involve the early cell biological alterations in pancreatic acinar cells.
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002199:Capillary Permeability; D002351:Carrageenan; D002401:Cathepsin B / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000209:etiology; D005260:Female; D005528:Foot; D006614:Hindlimb; D007705:Kinins / Q000037:antagonists & inhibitors*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010182:Pancreatic Diseases / Q000209:etiology; D010195:Pancreatitis / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D007705:Kinins; D002351:Carrageenan; D000681:Amylases; D002401:Cathepsin B