Combination angiotensin converting enzyme and direct renin inhibition in heart failure following experimental myocardial infarction.

Abstract

AIMS:

Diminishing the activity of the renin-angiotensin system (RAS) plays a pivotal role in the treatment of heart failure. In addition to angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers, direct renin inhibition has emerged as a potential adjunctive treatment to conventional RAS blockade. We sought to determine the effectiveness of this strategy after myocardial infarction (MI) in the setting of preexisting hypertension, a common premorbid condition in patients with ischemic heart disease.

METHODS AND RESULTS:

Ten-week-old female heterozygous hypertensive (mRen-2)27 transgenic rats (Ren-2), were randomized to one of five groups (n = 8 per group); sham, MI, MI + aliskiren, MI + lisinopril and MI + combination lisinopril and aliskiren. Cardiac function was assessed by echocardiography and in vivo cardiac catheterization. Untreated MI animals developed heart failure with hypotension, dilation, reduced ejection fraction (EF), and raised left ventricular end-diastolic pressure (LVEDP). Treatment with single agent treatment had only modest effect on cardiac function though combination therapy was associated with significant improvements in EF and LVEDP when compared to untreated MI animals (P < 0.05). Histologic analysis demonstrated increase extracellular matrix deposition and cardiomyocyte hypertrophy in the noninfarct region of all MI groups when compared with sham operated animals (P < 0.05) that was reduced by ACE inhibitor monotherapy and combination treatment but not by aliskiren alone.

CONCLUSION:

In a hypertensive rat model that underwent experimental MI, EF, and LVEDP, key functional indices of heart failure, were improved by treatment with combination ACE and direct renin inhibition when compared with either agent used alone.

• Authors: K A Connelly, A Advani, S Advani, Y Zhang, K Thai, S Thomas, H Krum, D J Kelly, R E Gilbert
• Journal: Cardiovascular therapeutics (Cardiovasc Ther) Vol. 31 Issue 2 Pg. 84-91 (Apr 2013) ISSN: 1755-5922 [Electronic] England
• PMID: 21884026 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Amides
• Angiotensin-Converting Enzyme Inhibitors
• Fumarates
• aliskiren
• Lisinopril
• Renin

Topics

• Amides (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Cardiac Catheterization
• Disease Models, Animal
• Drug Therapy, Combination
• Echocardiography
• Female
• Fumarates (pharmacology)
• Heart Failure (diagnosis, drug therapy, etiology, metabolism, physiopathology)
• Hypertension (complications)
• Lisinopril (pharmacology)
• Myocardial Infarction (complications, metabolism, physiopathology)
• Myocardium (pathology)
• Random Allocation
• Rats
• Rats, Transgenic
• Recovery of Function
• Renin (antagonists & inhibitors, metabolism)
• Renin-Angiotensin System (drug effects)
• Stroke Volume (drug effects)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)
• Ventricular Remodeling (drug effects)