Effects of a Bradykinin Receptor Antagonist (HOE140) on Taurocholate-Induced Acute Pancreatitis in Rats

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Abstract
The effect of a potent and long-acting brady-kinin B2-receptor antagonist (HOE 140) on acute pancreatitis induced by retrograde infusion of trypsin and taurocholate into the pancreatic duct was studied in rats. HOE 140 was administered subcutaneously immediately before and 3 h after the induction of pancreatitis and the systemic blood pressure, ascites volume, serum amylase, 24-h survival rate, and pathology of the pancreas were evaluated. Plasma concentrations of bradykinin increased significantly 15 min after the induction of pancreatitis and decreased to basal levels at 90 min. HOE140 (O.1 mg/kg) alleviated hypotension developing immediately after the induction of pancreatitis and reduced the ascites volume. The 24-h survival rate in rats treated with 0.1 mg/kg HOE 140 (70.3%) was significantly higher than that in controls (35.6%). Treatment with 0.01, 0.3, 1.0, and 3.0 mg/kg of HOE 140, however, had no beneficial effect on the survival rate. Ascites volume, serum amylase, and pa thology of the pancreas at 24 h were not improved by treatment with HOE 140. These data suggest that HOE 140 may improve the survival rate by maintaining hemody-namics in the early stage of experimental acute pancreatitis.

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