Kinin Precursor in Experimental Pancreatitis ∗

Abstract

Interest continues regarding the role of -inin peptides as humoral mediators in acute pancreatitis. Plasma is an ample substrate for kinin, which can be activated from its precursor state—bound to alpha 2 globulin—by either trypsin or kallikrein. These enzymes, in turn, are normally present in the pancreas and are activated during the cell necrosis of acute pancreatitis. Well-known pharmacologic actions of kinins include pain production, vasodilatation, increased vascular permeability, hypotension, smooth muscle stimulation, and leukocyte aggregation. All of these are characteristically found during the course of acute pancreatitis.

Direct measurement of plasma kinin was extremely difficult and for this reason studies were carried out on the component parts of the kinin system. We previously reported the finding of increased kinin inhibitors during the course of experimental pancreatitis (1). Significant changes in the level of kinin precursors would add weight to the evidence indicating the kinin system in the pathologic physiology of acute pancreatitis.

Method. Ten splenectomized mongrel dogs were anesthetized with sodium pentobarbital (30 mg/kg of body wt.) and both femoral veins were cannulated, one for the removal of blood and the other for injection of serum albumin ¹³¹I. Splenectomy was carried out 2 weeks previously to decrease the influence of splenic sequestration on the circulating blood volume. Pancreatitis was induced by intraductal infusion at 40 cm water pressure of a 20 ml mixture of 4% sodium taurocholate and 400,000 units of trypsin, adjusted to pH 8. Trypsin was previously assayed on a benzyl arginine ethyl ester substrate. Plasma volume was determined before operation and at 2, 4, and 6 hr after induction of pancreatitis using a Volemetron apparatus (Ames Company, Elkhart, Indiana). Hematocrit was determined by the micromethod. Plasma kininogen was determined by the method of Diniz and Carvalho (2) in which denatured plasma is exposed to an excess of trypsin, dried under pressure, and the residue resuspended in saline.