title: Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.
abstract: OBJECTIVE
  To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS).
  
  
  METHODS
  6 healthy Beagles.
  
  
  METHODS
  2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7.
  
  
  RESULTS
  High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C.
  
  
  CONCLUSIONS
  In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.
authors.forename: Marisa K
authors.initials: MK
authors.lastname: Ames
authors.forename: Clarke E
authors.initials: CE
authors.lastname: Atkins
authors.forename: Seunggon
authors.initials: S
authors.lastname: Lee
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Lantis
authors.forename: James R
authors.initials: JR
authors.lastname: zumBrunnen
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004285:Dogs / Q000502:physiology*; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000450:Aldosterone; D004656:Enalapril; D005665:Furosemide; D007703:Peptidyl-Dipeptidase A; C044946:benazepril