title: Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.
abstract: BACKGROUND
  Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown.
  
  
  OBJECTIVE
  To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior to and 2, 12 and 24 h after benazepril administration, each horse received intravenous (i.v.) boluses of ANG-I at 20, 60 and 200 ng/kg. Attenuation of the systolic arterial pressure (SBP) response to ANG-I and serum ACE activity were quantified and expressed as percentage of inhibition.
  
  
  RESULTS
  There was a significant effect of benazepril dose (P = 0.004) and time (P = 0.004) on the percentage of inhibition of the systolic pressor response to ANG-I. Regardless of benazepril dose, the percentage of inhibition was significantly greater 2 h after administration of benazepril compared with 12 and 24 h. At an ANG-I dose of 20 ng/kg, the percentage of inhibition after administration of benazepril at 1 mg/kg bwt (46.6 ± 18.9%) was significantly greater than that achieved after 0.5 mg/kg bwt (19 ± 14%) but not significantly different from that achieved at higher doses of benazepril. Benazepril doses ≥1 mg/kg bwt resulted in serum ACE inhibition of at least 90%.
  
  
  CONCLUSIONS
  Small sample size and resulting low statistical power.
  
  
  CONCLUSIONS
  Attenuation of the rise in SBP in response to ANG-I after administration of benazepril is modest in horses despite adequate serum ACE inhibition. A dose of 1 mg/kg bwt would be recommended for future investigations of benazepril for the management of cardiovascular diseases in horses.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors.forename: T
authors.initials: T
authors.lastname: Afonso
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors.forename: S
authors.initials: S
authors.lastname: Giguère
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors.forename: G
authors.initials: G
authors.lastname: Rapoport
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Coleman
mesh_terms: D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C044946:benazepril
keywords: ACE inhibitor; cardiology; horse; pressure response to angiotensin