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 enzyme 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.