Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.
BACKGROUND
Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown.


OBJECTIVES
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.


STUDY DESIGN
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%.


MAIN LIMITATIONS
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.
['Afonso|T|T|', 'Giguère|S|S|', 'Rapoport|G|G|', 'Brown|S A|SA|', 'Coleman|A E|AE|']
D000284:Administration, Oral D000803:Angiotensin I D000806:Angiotensin-Converting Enzyme Inhibitors D000818:Animals D001552:Benzazepines D001794:Blood Pressure D004305:Dose-Response Relationship, Drug D005260:Female D006736:Horses D007703:Peptidyl-Dipeptidase A D013997:Time Factors
horse ACE inhibitor cardiology pressure response to angiotensin