Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.
Abstract: 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.
© 2016 EVJ Ltd.
Publication Date: 2016-07-11 PubMed ID: 27224673DOI: 10.1111/evj.12593Google Scholar: Lookup
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- Clinical Trial
- Journal Article
Summary
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The research study seeks to identify the effective dosage of benazepril in inhibiting angiotensin-converting enzyme activity in horses. It particularly investigates the impact of benazepril in reducing the blood pressure response caused by angiotensin I in healthy adult horses.
Research Methodology
- An experimental study design was used with a sample size of five healthy horses. These horses were set up for direct blood pressure measurements.
- Four doses of Benazepril (0.5, 1, 2 and 4 mg/kg bwt) were administered orally to each horse with a 7-day rest period in between each dose.
- Before and after 2, 12 and 24 hours of administering the benazepril, each horse was given intravenous doses of angiotensin I (20, 60 and 200 ng/kg).
- The research looked at the attenuation in systolic arterial pressure response to the angiotensin I and the serum angiotensin-converting enzyme activity. These were quantified and recorded as the percentage of inhibition.
Key Findings
- The study found that both the dose of Benazepril and the time of its administration had a significant impact on the inhibition of systolic pressor response to Angiotensin I.
- The level of inhibition was higher 2 hours after Benazepril administration as compared to 12 and 24 hours later, regardless of the dose administered.
- A dose of 1 mg/kg bwt of Benazepril presented a higher inhibition level than a dose of 0.5 mg/kg bwt, while levels were not significantly different from those achieved at higher doses.
- Benazepril doses equal to or above 1 mg/kg bwt resulted in at least 90% serum angiotensin-converting enzyme inhibition.
- The attenuation effect on systolic blood pressure response to the angiotensin I was modest in horses, despite adequate serum angiotensin-converting enzyme inhibition.
Conclusion
- Despite the small sample size and the attendant low statistical power of this study, the findings suggested that a dose of 1mg/kg bwt of benazepril could be recommended for future investigations in managing cardiovascular diseases in horses.
Cite This Article
APA
Afonso T, Giguère S, Rapoport G, Brown SA, Coleman AE.
(2016).
Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.
Equine Vet J, 49(3), 358-362.
https://doi.org/10.1111/evj.12593 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, USA.
MeSH Terms
- Administration, Oral
- Angiotensin I / administration & dosage
- Angiotensin I / pharmacology
- Angiotensin-Converting Enzyme Inhibitors / pharmacology
- Animals
- Benzazepines / pharmacology
- Blood Pressure / drug effects
- Dose-Response Relationship, Drug
- Female
- Horses / physiology
- Peptidyl-Dipeptidase A / blood
- Peptidyl-Dipeptidase A / metabolism
- Time Factors
Citations
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