Actions of ACE

• Angiotensin-converting enzyme (ACE) inhibitors inhibit ACE (present in the endothelia of the small blood vessels of the lungs, kidneys and other tissues).
• ACE has vital roles in both the renin-angiotensin-aldosterone (RAA) system and kallikrein-kinin (bradykinin) system:
  • Renin is released from the juxtaglomerular apparatus in the kidney in response to:
    • Decreased renal blood flow.
    • Decreased sodium chloride delivery to the macula densa (sodium depletion, natriuresis).
    • Beta-adrenergic stimulation.
• Renin converts angiotensinogen (made in the liver) into angiotensin I ( a precursor molecule which is mainly inactive).
• ACE converts angiotensin I (a precursor molecule which is mainly inactive) to the active hormone angiotensin II.
• ACE catalyses breakdown of bradykinin, a hormone that promotes vasodilation via nitric oxide and prostaglandins, and natriuresis in the kidney.

Actions of angiotensin II

Effects of ACE inhibitors

ACE inhibitors available

ACE inhibitors and preclinical cardiac disease

Clinical concerns for the use of ACE inhibitors

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• O'Grady M R, O'Sullivan M L, Minors S L et al (2009) Efficacy of Benazepril Hydrochloride to Delay the Progression of Occult Dilated Cardiomyopathy in Doberman Pinschers. J Vet Intern Med 23 (5), 977-983 PubMed.
• Atkins C E, Keene B W, Brown W A et al (2007) Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. J Am Vet Med Assoc 231 (7), 1061-1069 PubMed.
• Besche B, Chetboul V, Lachaud Lefay M P et al (2007) Clinical evaluation of imidapril in congestive heart failure in dogs: results of the EFFIC study. J Small Anim Pract 48 (5), 265-270 PubMed.
• Lefebvre H P, Jeunesse E, Laroute V et al (2006) Pharmacokinetic and pharmacodynamic parameters of ramipril and ramiprilat in healthy dogs and dogs with reduced glomerular filtration rate. J Vet Intern Med 20 (3), 499-507 PubMed.
• Amberger C, Chetboul V, Bomassi E et al (2004) Comparison of the effects of imidapril and enalapril in a prospective, multicentric, randomized trial in dogs with naturally acquired heart failure. J Vet Cardiol 6 (2), 9-16 PubMed.
• BENCH (BENazepril in Canine Heart disease) Study Group, Pouchelon J L, King J et al (2004) Long-term tolerability of benazepril in dogs with congestive heart failure. J Vet Cardiol 6 (1), 7-13 PubMed.
• Toutain P L & Lefèbvre H P (2004) Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors. J Vet Pharmacol Therap 27 (6), 515-525 PubMed.
• Atkins C E, Brown W A, Coats J R et al (2002) Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation. J Am Vet Med Assoc 221 (5), 654-658 PubMed.
• Kvart C, Häggström J, Pedersen H D et al (2002) Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. J Vet Intern Med 16 (1), 80-88 PubMed.
• The BENCH (BENazepril in Canine Heart disease) Study Group (1999) The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. J Vet Cardiol 1 (1), 7-18 PubMed.
• Davidson G, Horeish C (1999) Enalapril maleate. Comp Contin Educ Pract Vet 21 (12), 1118-1121 VetMedResource.
• Lefebvre H P, Laroute V, Concordet D et al (1999) Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites. J Vet Intern Med 13 (1), 21-7 PubMed.
• Boswood A (1998) Rationale for the use of drugs in the treatment of cardiovascular disease. 2. Vasodilators. In Practice 20 (2), 55-63 VetMedResource.
• Ettinger S J, Benitz A M, Ericsson G F et al (1998) Effects of enalapril malaete on survival of dogs with naturally acquired heart failure. The Long-Term Investigation of Veterinary Enalapril (LIVE) Study Group. J Am Vet Med Assoc 213 (11), 1573-1577 PubMed.
• Hamlin R L & Nakayama T (1998) Comparison of some pharmacokinetic parameters of 5 angiotensin-converting enzyme inhibitors in normal beagles. J Vet Intern Med 12 (2), 93-95 PubMed.
• King J N, Maurer M, Morrison C A et al (1997) Pharmacokinetics of the angiotensin-converting-enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, in dogs. Xenobiotica 27 (8), 819-829 PubMed.
• Boswood A (1996) Rationale for the use of drugs in the treatment of cardiovascular disease. 1. Diuretics. In Practice 18 (10), 469-476 VetMedResource.
• The IMPROVE Study Group (1995) Acute and short-term hemodynamic, echocardiographic, and clinical effects of enalapril maleate in dogs with naturally acquired heart failure: Results of the Invasive Multicenter PROspective Veterinary Evaluation of Enalapril Study. J Vet Intern Med 9 (4), 234-242 PubMed.

Other sources of information

• Opie L H, Poole-Wilson P A, Pfeffer M A (2005) Angiotensin-Converting Enzyme (ACE) Inhibitors, Angiotenin-II Receptor Blockers (ARBs), and Aldosterone Antagonists. In: Drugs for the Heart, 6th ed., Eds: L. H. Opie & B, J, Gersh. Elsevier Saunders, Philadelphia.
• Lombard C (2000) 10th ESVIM Congress, Neuchatel.