[Effect of 8-week administration of enalapril plus additional 2-week administration of furosemide on heart rate and exocrine pancreas secretion in dogs].
Alteration of pancreatic secretion could be a pathogenetic factor for generation of an acute pancreatitis after administration of angiotensin-converting-enzyme (ACE) inhibitors. Therefore in 6 conscious dogs (weight 10-12 kg) with chronic gastric and duodenal fistulas according to Thomas, we studied single-blind, placebo-controlled and randomized the effect of a long-term (74 d) daily oral administration of 5 mg of the ACE inhibitor enalapril and of additionally daily oral administration of the diuretic furosemide from the 60th day on the secretin- (20.5 pmol/kg/h) and caerulein- (7.4, 14.8, 29.6, 59, and 118 pmol/kg/h) stimulated pancreatic bicarbonate and protein secretion at day 1, 29, 57, 60, and 74 after beginning of enalapril administration. Heart rate was measured daily and during the experiments. Neither enalapril nor enalapril plus furosemide significantly altered heart rate. The hormonally stimulated pancreatic bicarbonate secretion was significantly (p < 0.05) increased at day 57, 60, and 74 by 353%, 397%, and 79%. The hormonally stimulated pancreatic protein secretion was also distinctly increased, although not reaching statistical significance. The present study shows, that a long-term administration of therapeutic doses of enalapril +/-furosemide is capable to enhance the pancreatic bicarbonate secretion. Whether this altered pancreatic secretion can be taken for a primary origin of the observed cases of acute pancreatitis after therapeutic administration of enalapril is uncertain but not refutable.
Niebergall-Roth
E
E
IV. Medizinische Universitätsklinik (Schwerpunkt Gastroenterologie), Klinikum Mannheim, Universität Heidelberg.
Teyssen
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S
Weber
T
T
Singer
M V
MV
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011897:Random Allocation; D012633:Secretin / Q000494:pharmacology; D016037:Single-Blind Method; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001639:Bicarbonates; D004232:Diuretics; D011506:Proteins; D012633:Secretin; D004656:Enalapril; D005665:Furosemide; D002108:Ceruletide