Selected Publication:
Griesbacher, T; Tiran, B; Lembeck, F.
Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140.
Br J Pharmacol. 1993; 108(2):405-411
Doi: 10.1111/j.1476-5381.1993.tb12817.x
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- Leading authors Med Uni Graz
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Griesbacher Thomas
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Lembeck Fred
- Co-authors Med Uni Graz
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Tiran Beate
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- Abstract:
- 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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Acute Disease -
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Animals -
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Bradykinin - analogs and derivatives
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Edema - physiopathology
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Female - physiopathology
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Hematocrit - physiopathology
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Hypotension - physiopathology
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Pancreas - enzymology
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Pancreatitis - blood
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Protease Inhibitors - pharmacology
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Rats - pharmacology
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Rats, Sprague-Dawley - pharmacology