1. The novel
bradykinin antagonist,
HOE 140, completely blocked the fall in rabbit blood pressure caused, not only by i.v.
bradykinin, but also by i.v.
kallikrein. This shows that both the effects of exogenously administered
bradykinin and those of endogenously released
kinins are antagonized by
HOE 140. 2.
Acute pancreatitis was induced in rats by i.v. infusion of the
cholecystokinin analogue,
caerulein. This treatment resulted in massive oedema of the pancreas, increased activities of
amylase and
lipase in serum and a characteristic, biphasic fall in blood pressure. 3.
HOE 140 prevented the
caerulein-induced pancreatic oedema and the second phase of
hypotension whereas
NPC 349, a widely used, but short-acting,
bradykinin antagonist did not show a significant inhibition.
HOE 140, in contrast to its inhibitory effects on
caerulein-induced pancreatic oedema and
hypotension, significantly augmented the increases in
amylase and
lipase activities in serum. 4. It is concluded that in this model of
acute pancreatitis, the release of
kinins induces pancreatic oedema and
hypotension. Prevention by
HOE 140 of the
kinin-induced oedema allows the pancreatic
enzymes to leave the tissue without hindrance and thus will diminish subsequent pathological events. It is suggested that the results obtained with the highly potent and long-acting
bradykinin antagonist,
HOE 140, provide a pharmacological basis for a clinical trial in
acute pancreatitis.