Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs

  1. J. P. MOCHEL1,
  2. M. PEYROU2,
  3. M. FINK3,
  4. G. STREHLAU4,
  5. R. MOHAMED2,
  6. J. M. GIRAUDEL5,
  7. B. PLOEGER6,
  8. M. DANHOF6

Article first published online: 8 MAY 2012

DOI: 10.1111/j.1365-2885.2012.01406.x

Issue

Journal of Veterinary Pharmacology and Therapeutics

Journal of Veterinary Pharmacology and Therapeutics

Volume 36, Issue 2, pages 174–180, April 2013

Additional Information

How to Cite

MOCHEL, J. P., PEYROU, M., FINK, M., STREHLAU, G., MOHAMED, R., GIRAUDEL, J. M., PLOEGER, B. and DANHOF, M. (2013), Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs. Journal of Veterinary Pharmacology and Therapeutics, 36: 174–180. doi: 10.1111/j.1365-2885.2012.01406.x

Author Information

  1. 1

    Department of Drug Metabolism and Pharmacokinetics, Novartis Campus St. Johann, Basel, Switzerland

  2. 2

    Department of Bioanalytics, Novartis Centre de Recherche Sante Animale SA, Aubin, Switzerland

  3. 3

    Department of Modeling and Simulation, Novartis Campus St. Johann, Basel, Switzerland

  4. 4

    Department of Drug Efficacy, Novartis Animal Health, Basel, Switzerland

  5. 5

    Department of Research and Development, Novartis Animal Health Australasia Pty Limited, Yarrandoo, NSW, Australia

  6. 6

    Department of Pharmacology, Leiden-Amsterdam Center for Drug Research, Leiden, The Netherlands

* Dr Jonathan P. Mochel, Novartis Campus St. Johann, WSJ-27.6, 4056 Basel, Switzerland. E-mail: jonathan.mochel@novartis.com

  1. The results were partially presented in abstract form at the American College of Veterinary Internal Medicine Forum, June 16, 2011, Denver, CO, USA.

Publication History

  1. Issue published online: 8 MAR 2013
  2. Article first published online: 8 MAY 2012
  3. (Paper received 26 October 2011; accepted for publication 9 April 2012)

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Mochel, J. P., Peyrou, M, Fink, M, Strehlau, G, Mohamed, R, Giraudel, J. M., Ploeger, B, Danhof, M. Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs. J. vet. Pharmacol. Therap. 36, 174–180.

In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC24 hours) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC24 hours of plasma renin activity (+90%), angiotensin I (+43%), and AII (−53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.

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