Effect of kinin inhibition in experimental acute pancreatitis.
Lerch, M. M., H. Weidenbach, T. M. Gress, and G. Adler.
Department of Medicine I, Ulm University, 89070 Ulm, Germany
APStracts 2:0083G, 1995.
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, by
intraductal injection of sodiumtaurocholate, or by 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
(0.1mg/kg, q5h). Effective kinin inhibition had no effect on
pancreatitis-associated mortality, on the extent of morphologic
damage and inflammation, or on the intracellular distribution of
lysosomal hydrolases. Pancreatic edema was only reduced in caerulein
-induced pancreatitis, the only model where 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.
Received 8 June 1994; accepted in final form 21 March 1995.
APS Manuscript Number G221-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.