title: Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.
abstract: 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 (AUC) 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 AUC 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.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Novartis Campus St. Johann, Basel, Switzerland. jonathan.mochel@novartis.com
authors.forename: J P
authors.initials: JP
authors.lastname: Mochel
authors.forename: M
authors.initials: M
authors.lastname: Peyrou
authors.forename: M
authors.initials: M
authors.lastname: Fink
authors.forename: G
authors.initials: G
authors.lastname: Strehlau
authors.forename: R
authors.initials: R
authors.lastname: Mohamed
authors.forename: J M
authors.initials: JM
authors.lastname: Giraudel
authors.forename: B
authors.initials: B
authors.lastname: Ploeger
authors.forename: M
authors.initials: M
authors.lastname: Danhof
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001552:Benzazepines / Q000494:pharmacology*; D004285:Dogs / Q000097:blood* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; C044946:benazepril