title: Evaluation of the effect of an angiotensin-converting enzyme inhibitor, alacepril, on drug-induced renin-angiotensin-aldosterone system activation in normal dogs.
abstract: BACKGROUND
  To determine if alacepril, an angiotensin-converting enzyme inhibitor, has a long duration of action for inhibition of drug-induced renin-angiotensin-aldosterone system (RAAS) activation in normal dogs.
  
  
  METHODS
  Five healthy laboratory dogs were used in this study.
  
  
  METHODS
  Each dog received amlodipine (0.5 mg/kg, q12h, p.o.) for 14 days, followed by amlodipine (0.5 mg/kg, q12h, p.o.) and alacepril (1.5 mg/kg, q12h, p.o.) for 56 days. Blood pressure (systolic blood pressure [SBP]; mean blood pressure; and diastolic blood pressure), heart rate, and urinary aldosterone-to-creatinine ratio (UAld:Cre), as an indicator of RAAS activation, were measured on days -14, 0 (baseline [BL]), 1, 7, 14, 28, and 56.
  
  
  RESULTS
  SBP decreased by 10% (p=0.08), and UAld:Cre increased significantly (p=0.04) relative to the BL level after administration of amlodipine. SBP increased after 14 days of alacepril administration relative to BL (p=0.97), and statistically significant increase was first observed on day 28 (p=0.02). Heart rate significantly decreased after alacepril administration on days 14, 28, and 56 (p=0.02). UAld:Cre significantly decreased after alacepril administration on days 14 and 28 (p≤0.03) relative to the BL level but increased on day 56 such that the difference was no longer significant (p=0.32).
  
  
  CONCLUSIONS
  These incomplete and temporary pharmacological blockade of RAAS activation by alacepril suggest that aldosterone breakthrough may have occurred.
  
  
  CONCLUSIONS
  Alacepril inhibited activation of RAAS in the short term but is not expected to have a long duration of action.
authors.affiliation: Division of Therapeutic Sciences, Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan. Electronic address: asakatani0805@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Sakatani
authors.affiliation: Division of Therapeutic Sciences, Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Division of Therapeutic Sciences, Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takemura
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril; C046835:alacepril
keywords: Aldosterone-to-creatinine ratio; Blood pressure; Canine; Heart rate