Evaluation of the effect of an angiotensin-converting enzyme inhibitor, alacepril, on drug-induced renin-angiotensin-aldosterone system activation in normal dogs

Introduction: To determine if alacepril, an angiotensin-converting en zyme inhibitor, has a long duration of action for inhibition of drug-induced renin-angiotensin-aldosterone system (RAAS) activation in normal dogs. Animals: Five healthy laboratory dogs were used in this study. Materials and Methods: Each dog received amlodipine (0.5 mg/kg, q12h, p.o.) for 14 days, followed by amlodipine (0.5 mg/kg, q12h, p.o.) and alacepril (1.5 mg/kg, q12h, p.o.) for 56 days. Blood pressure (systolic blood pressure [SBP]; mean blood pressure; and diastolic blood pressure), heart rate, and urinary aldosterone-to-creatinine ratio (UAld:Cre), as an indicator of RAAS activation, were measured on days -14, 0 (baseline [BL]), 1, 7, 14, 28, and 56. Results: SBP decreased by 10% (p=0.08), and UAld:Cre increased significantly (p=0.04) relative to the BL level after administration of amlodipine. SBP increased after 14 days of alacepril administration relative to BL (p=0.97), and statistically significant increase was first observed on day 28 (p=0.02). Heart rate significantly decreased after alacepril administration on days 14, 28, and 56 (p=0.02). UAld:Cre significantly decreased after alacepril administration on days 14 and 28 (p<0.03) relative to the BL level but increased on day 56 such that the difference was no longer significant (p=0.32). Discussion: These incomplete and temporary pharmacological blockade of RAAS activation by alacepril suggest that aldosterone breakthrough may have occurred. Conclusions: Alacepril inhibited activation of RAAS in the short term but is not expected to have a long duration of action. (C) 2016 Elsevier B.V. All rights reserved.