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
bradykinin receptor antagonist on
bradykinin and
beta-endorphin release and on hemodynamic changes during
acute pancreatitis.
Pancreatitis was induced by the injection of autologous bile mixed with
trypsin into the main pancreatic duct after
ligation of the accessory duct. Serum
bradykinin and plasma
beta-endorphin levels and cardiovascular function were measured. Twelve dogs (control group) were given 10 ml/kg/h of
lactate Ringer's solution intravenously beginning 1 h before the induction of
pancreatitis and continuing throughout the experiments. Six dogs received an
intravenous infusion of 0.6 mg/kg/h of a new
bradykinin receptor antagonist,
HOE 140, D-Arg-[Hyp3, Thi5, D-
Tic, Oic8]-
bradykinin, in
lactate Ringer's solution soon after the induction of
pancreatitis. Six of twelve dogs in the control group, and none of the six dogs in the
bradykinin receptor antagonist group, died during the experiments. Serum
bradykinin levels in both groups increased until 1 h after the induction of
pancreatitis, but thereafter the levels in the
bradykinin receptor antagonist group decreased gradually until 5 h after induction, and levels were significantly lower than those in the control group (p < 0.05). Plasma
beta-endorphin levels in the control group increased significantly, to 291.8 pg/ml (+/- 6.6 SEM) 5 h after the induction of
pancreatitis, from the mean levels of 47.8 pg/ml before the induction of
pancreatitis, while the mean
beta-endorphin level in the
bradykinin receptor antagonist group did not increase after the induction of
pancreatitis. Infusion of the
bradykinin receptor antagonist improved survival rates,
hypotension, myocardial depression, and plasma
lactate, suggesting that the
bradykinin receptor antagonist inhibited the release of
bradykinin and
beta-endorphin, which contributed to the clinical improvement.