Ramipril and telmisartan exhibit differential effects in cardiac pressure overload-induced hypertrophy without an additional benefit of the combination of both drugs.

Abstract

OBJECTIVES:

We aimed to characterize different cellular effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin 1 (AT1) receptor blockers (ARBs) as mono- or combination therapy in cardiac pressure overload. Methods and

RESULTS:

C57B1/6 mice received either the ACEI ramipril (2.5 mg/kg body weight), the ARB telmisartan (20 mg/kg body weight), or the combination. In all groups, pressure overload was induced by transverse aortic constriction (TAC). Cardiac hypertrophy (heart weight/tibia length) induced by TAC was reduced in all 3 treatment groups, with the most pronounced effect in the telmisartan group. The cardiomyocyte short-axis diameter and cardiac fibrosis were increased by TAC and similarly reduced by ACEI, ARB, and the combination therapy. The TAC-induced increase in the number of proliferating Ki67(pos) cardiomyocytes and noncardiomyocytes was reduced more potently by ACEI than by ARB. Four days of drug treatment induced a significant increase in Scal(pos)/VEGFR1(pos) endothelial progenitor cells (EPCs) in all animals in the treated SHAM groups. After 1 day of aortic constriction, only ramipril increased EPC numbers; after 5 weeks, telmisartan monotherapy did not change the EPC levels compared to vehicle or the combination therapy but raised it compared to ramipril. Neither TAC nor one of the therapies changed the number of cardiac capillaries per cardiomyocytes.

CONCLUSIONS:

ACE inhibition and AT1 receptor blockade have beneficial effects in remodeling processes during cardiac pressure overload. There are small differences between the 2 therapeutical approaches, but the combination therapy has no additional benefit.

• Authors: Patrick Müller, Andrey Kazakov, Alexander Semenov, Philippe Jagoda, Erik B Friedrich, Michael Böhm, Ulrich Laufs
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 18 Issue 1 Pg. 87-93 (Jan 2013) ISSN: 1940-4034 [Electronic] United States
• PMID: 22368266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Benzimidazoles
• Benzoates
• Ramipril
• Telmisartan

Topics

• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Animals
• Benzimidazoles (administration & dosage, therapeutic use)
• Benzoates (administration & dosage, therapeutic use)
• Blood Pressure (physiology)
• Cardiomegaly (prevention & control)
• Drug Therapy, Combination
• Endothelial Cells (drug effects)
• Fibrosis
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (pathology)
• Ramipril (administration & dosage, therapeutic use)
• Stem Cells (drug effects)
• Telmisartan