Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In a previous investigation, Hoe 140, a specific and potent bradykinin B2 receptor antagonist, prevented the pancreatic oedema and the hypotension observed during acute experimental pancreatitis; however, it augmented the associated rises in the serum activities of pancreatic enzymes. Therefore, we have now investigated the consequences of the pancreatic oedema for the fate of activated enzymes released into the tissue during the course of acute pancreatitis. 2. Acute oedematous pancreatitis was induced in rats, pretreated with captopril (50 mumol kg-1, i.p.), by hyperstimulation of the exocrine function of the pancreas with the cholecystokinin analogue, caerulein (4 nmol kg-1 h-1, i.v.), for up to 120 min. 3. Pancreatic oedema began to develop 10 min after the start of the caerulein infusion, reached a maximum within about 45 min, and then declined slightly. The development of the oedema parallelled the second phase of the caerulein-induced fall in blood pressure found in earlier experiments. No further extravasation of plasma proteins occurred during the 2nd hour of the caerulein infusion. The oedema formation was completely blocked in animals pretreated with the bradykinin receptor antagonist, Hoe 140 (100 nmol kg-1, s.c.). Pretreatment with aprotinin or soy bean trypsin inhibitor did not result in a significant inhibition of the oedema. 4. The haematocrit of animals with experimental pancreatitis showed a pronounced increase which started 10 min after the start of the caerulein infusion and reached maximal values at 60 min. The changes in haematocrit showed a reduction in total blood volume of 28% due to a 48% loss of plasma. This effect was completely blocked by Hoe 140. 5. In rats with caerulein-induced pancreatitis, there was a time-dependent increase in the activities of amylase and lipase in blood serum as well as in the pancreas. Pretreatment with Hoe 140 greatly augmented the caerulein-induced rise in enzyme activities in blood serum but potently attenuated it in the pancreas. The activities of trypsin in both the blood serum and the pancreas were below or near the limit of detection in all experimental groups.6. It is concluded that the second phase of hypotension in this model of acute pancreatitis is due to the liberation of kinins which cause a massive loss of blood plasma into the pancreas and into the retroperitoneal space. Activated enzymes are trapped in the pancreas, at least in part, by the oedema of the gland. Treatment with Hoe 140 prevents the oedema formation and greatly facilitates the egress of activated enzymes from the pancreas.
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PMID:Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140. 844 91

It has been found earlier that the bradykinin antagonist, icatibant (Hoe 140), prevents the pancreatic oedema and the ensuing hypotension and haemoconcentration, and facilitates the removal of activated enzymes form the tissue during caerulein-induced acute pancreatitis. For a potential therapeutic use of the compound in clinical situations it is essential to investigate whether the associated increase in enzyme activities in the blood serum has any adverse effects on the pancreas itself or on other organs. Normal amylase secretion into the biliopancreatic duct stimulated by a low dose of caerulein (0.4 nmol kg-1 h-1, i.v.) was not affect by icatibant (100 nmol kg-1, s.c.) Acute pancreatitis, induced by a high dose of caerulein (4 nmol kg-1 h-1 for 2 h, i.v.), resulted in elevations in the activities of amylase and lipase in the pancreatic tissue and in the blood serum lasting for at least 4 h after the end of the caerulein infusion. While the rise in enzyme activities in the blood serum was augmented in icatibant-treated rats only at the end of the caerulein-infusion, the enzyme accumulation in the pancreas was significantly reduced by icatibant for at least 4 h after the end of the caerulein infusion. The secretion of amylase and lipase into the biliopancreatic duct was significantly increased only during the first 20 min of acute pancreatitis; in rats pre-treated with icatibant, no significant increase could be observed. Twenty-four hours after induction of pancreatitis, a low-dose caerulein stimulation of the exocrine function of the pancreas led to a reduced but sustained secretion of amylase regardless of whether the animals had received icatibant or not. During the first 45 min of pancreatitis, blood glucose concentrations were significantly reduced, but returned to values not different from those obtained in saline-infused controls. This effect was not affected by icatibant. No changes in the response to an i.v. glucose tolerance test were found on the day after induction of acute pancreatitis. The serum activities of glutamic pyruvic transaminase and gamma-glutamyl transpeptidase determined up to 24 h after induction of pancreatitis were not different from saline controls. icatibant had no effect on the activities of these enzymes. It is concluded that during caerulein-induced acute pancreatitis normal exocrine secretion of pancreatic enzymes into the pancreatic duct ceases almost immediately. Pre-treatment with icatibant significantly reduces the accumulation of activated enzymes in the pancreatic tissue for several hours after induction of pancreatitis while a concomitant augmentation in enzyme activities in the blood serum lasts much shorter. There is no indication of adverse effects on the function of the endocrine or exocrine pancreas and that of the liver, either during the acute stages of pancreatitis or during the recovery period.
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PMID:Effects of the bradykinin antagonist, icatibant (Hoe 140), on pancreas and liver functions during and after caerulein-induced pancreatitis in rats. 875 Oct 86

The i.v. infusion of a low dose of the cholecystokinin agonist caerulein elicited a sustained secretion of amylase into the biliopancreatic duct of rats. Pretreatment with the bradykinin antagonist icatibant (Hoe-140) had no effect on unstimulated amylase release and did not affect caerulein-induced amylase secretion. An i.v. infusion of bradykinin in doses not producing a pancreatic oedema elicited an increase in pancreatic juice production lasting 20-40 min after the end of the infusion. This pro-secretory effect was also visible at higher doses in captopril-pretreated rats producing an oedema similar to that observed in caerulein-induced pancreatitis. Using the Monastral blue method, it was found that the kininase II blocker captopril induced an opening of endothelial gaps in pancreatic capillaries. This effect was blocked by icatibant suggesting that kinins are formed in the pancreas under basal conditions. Thus, kinins appear not to be involved in the regulation of the production of digestive enzymes. However, kinins may have a modulatory role in the production of pancreatic juice and in the microcirculatory regulation in the pancreas.
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PMID:Pathophysiological and possible physiological roles of kinins in the pancreas. 885 79