Combined angiotensin receptor blocker and ACE inhibitor on myocardial fibrosis and left ventricular stiffness in dogs with heart failure.

Abstract

Angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor (ACEI) each act in a different manner to prevent myocardial fibrosis and left ventricular (LV) stiffness in animals with pathways in the heart for generating ANG II as well as ACE. A model of pacing-induced congestive heart failure (CHF) was used to test the central hypothesis that ARB + ACEI prevents myocardial fibrosis and decreases LV stiffness to a greater extent than ARB or ACEI alone. Thirty-five dogs were assigned to the following treatment protocols on the 8th day of a 4-wk pacing schedule: 1) rapid ventricular pacing, 2) ARB (candesartan cilexetil, 1.5 mg.kg(-1).day(-1)) with pacing, 3) ACEI (enalapril, 1.9 mg.kg(-1).day(-1)) with pacing, 4) ARB (candesartan cilexetil, 0.75 mg.kg(-1).day(-1)) + ACEI (enalapril, 0.95 mg.kg(-1).day(-1)) with pacing, and 5) sham operation. The LV stiffness coefficient was significantly increased after rapid pacing but was significantly lower with ARB + ACEI than with ARB or ACEI alone. The collagen volume fraction and mRNA levels of collagen I and III, which were increased by rapid pacing, were significantly lower with ARB + ACEI than with ARB or ACEI alone. Thus ARB + ACEI prevents myocardial fibrosis and decreases LV stiffness during the progression of CHF compared with ARB or ACEI alone.

• Authors: Kaoru Funabiki, Katsuya Onishi, Kaoru Dohi, Takafumi Koji, Kyoko Imanaka-Yoshida, Masaaki Ito, Hideo Wada, Naoki Isaka, Tsutomu Nobori, Takeshi Nakano
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 287 Issue 6 Pg. H2487-92 (Dec 2004) ISSN: 0363-6135 [Print] United States
• PMID: 15548724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Benzimidazoles
• Biphenyl Compounds
• Collagen Type I
• Collagen Type III
• Tetrazoles
• Enalapril
• candesartan cilexetil
• Norepinephrine

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Biphenyl Compounds (pharmacology)
• Cardiac Volume (drug effects)
• Collagen Type I (genetics)
• Collagen Type III (genetics)
• Dogs
• Drug Therapy, Combination
• Enalapril (pharmacology)
• Fibrosis
• Gene Expression (drug effects)
• Heart Failure (drug therapy, pathology, physiopathology)
• Male
• Myocardium (pathology)
• Norepinephrine (blood)
• Tetrazoles (pharmacology)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)