EFFECTS OF BRADYKININ RECEPTOR ANTAGONIST ON THE RELEASE OF BETA-ENDORPHIN AND BRADYKININ AND ON HEMODYNAMIC-CHANGES IN A CANINE MODEL OF EXPERIMENTAL ACUTE-PANCREATITIS

Bradykinin and beta-endorphin increases during acute pancreatitis are thought to contribute to the development of hypotension and myocardial depression in acute pancreatitis. beta-Endorphin release is mediated by trypsin-like enzymes and bradykinin from the pituitary gland. This study was undertaken to investigate the effect of a long-acting bradyk inin receptor antagonist on bradykinin and beta-endorphin release and on hemodynamic changes during acute pancreatitis. Pancreatitis was ind uced by the injection of autologous bile mixed with trypsin into the m ain pancreatic duct after ligation of the accessory duct. Serum bradyk inin and plasma beta-endorphin levels and cardiovascular function were measured. Twelve dogs (control group) were given 10 ml/kg/h of lactat e Ringer's solution intravenously beginning 1 h before the induction o f pancreatitis and continuing throughout the experiments. Six dogs rec eived an intravenous infusion of 0.6 mg/kg/h of a new bradykinin recep tor antagonist, HOE 140, D-Arg-[Hyp(3), Thi(5), D-Tic, Oic(8)]-bradyki nin, in lactate Ringer's solution soon after the induction of pancreat itis. Six of twelve dogs in the control group, and none of the six dog s in the bradykinin receptor antagonist group, died during the experim ents. Serum bradykinin levels in both groups increased until 1 h after the induction of pancreatitis, but thereafter the levels in the brady kinin receptor antagonist group decreased gradually until 5 h after in duction, and levels were significantly lower than those in the control group (p < 0.05). Plasma beta-endorphin levels in the control group i ncreased significantly, to 291.8 pg/ml (+/-6.6 SEM) 5 h after the indu ction of pancreatitis, from the mean levels of 47.8 pg/ml before the i nduction of pancreatitis, while the mean beta-endorphin level in the b radykinin receptor antagonist group did not increase after the inducti on of pancreatitis. Infusion of the bradykinin receptor antagonist imp roved survival rates, hypotension, myocardial depression, and plasma l actate, suggesting that the bradykinin receptor antagonist inhibited t he release of bradykinin and beta-endorphin, which contributed to the clinical improvement.