Resumen de Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs
Marisa K. Ames, Clarke E. Atkins, Seunggon Lee, Andrea C. Lantis, James R. zumBrunnen
Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs Marisa K. Ames, DVM; Clarke E. Atkins, DVM; Seunggon Lee, DVM, PhD; Andrea C. Lantis, DVM; James R. zumBrunnen, MS Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. (Ames, Atkins, Lee, Lantis, zumBrunnen) Dr. Ames’ present address is the Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
Dr. Lee's present address is Choonghyun Animal Hospital, 191-2 Nonhyeon-ro, Gangnam-gu, Seoul, 135-080, Republic of Korea.
Dr. Lantis’ present address is Veterinary Emergency and Referral Group, 318 Warren St, Brooklyn, NY 11201.
Mr. zumBrunnen's present address is Department of Statistics, College of Natural Sciences, Colorado State University, Fort Collins, CO 80523.
Address correspondence to Dr. Ames (marisa.ames@colostate.edu).
OBJECTIVE To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS).
ANIMALS 6 healthy Beagles.
PROCEDURES 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days −1, 3, and 7; serum aldosterone concentration on days −2, −1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days −2, −1, 1, 3, and 7.
RESULTS High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.
