EFFECT OF AN 8 WEEK LASTING ADMINISTRATIO N OF ENALAPRIL PLUS A FOLLOWING 2 WEEK LASTING ADDITIONAL ADMINISTRATION OF FUROSEMIDE ON HEART-RATE AND PANCREATIC EXOCRINE SECRETION IN THE DOG

Alteration of pancreatic secretion could be a pathogenetic factor for generation of an acute pancreatitis after administration of angiotensi n-converting-enzyme (ACE) inhibitors. Therefore in 6 conscious dogs (w eight 10-12 kg) with chronic gastric and duodenal fistulas according t o Thomas, we studied single-blind, placebo-controlled and randomized t he effect of a long-term (74 d) daily oral administration of 5 mg of t he ACE inhibitor enalapril and of additionally daily oral administrati on 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 sti mulated 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 enal april 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 hormon ally stimulated pancreatic protein secretion was also distinctly incre ased, although not reaching statistical significance. The present stud y shows, that a long-term administration of therapeutic doses of enala pril +/- furosemide is capable to enhance the pancreatic bicarbonate s ecretion. Whether this altered pancreatic secretion can be origin of t he observed cases of acute pancreatitis after therapeutic administrati on of enalapril is uncertain but not refutable.