Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
Volume 18, Issue 1, Pages 87-93Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1074248411434773
Keywords
cardiac pressure overload; endothelial progenitor cells; ACE inhibition; angiotensin receptor blockade
Funding
- Boehringer/Ingelheim
- Hans & Gertie Fischer-Stiftung, Essen
- Deutsche Forschungsgemeinschaft [KFO 196]
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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 bodyweight), the ARB telmisartan (20 mg/kg bodyweight), 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.
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