© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Development of heart failure following isoproterenol administration in the rat: role of the renin–angiotensin system
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, D-93042 Regensburg, Germany
* Corresponding author. Tel. +49-941-944-7211; Fax +49-941-944-7213; E-mail: eckhard.kromer@klinik.uni-regensburg.de
Objective: High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin–angiotensin system using ramipril. Methods and Results: Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol+ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins. Conclusions: In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin–angiotensin system.
KEYWORDS ACE=angiotensin converting enzyme; cANP=c-terminal atrial natriuretic peptide (99-126); CTRL group=animals treated with vehicle; ISO group=animals treated with a single dose of isoproterenol; LV=left ventricle; RAM group=animals treated with isoproterenol and with ramipril
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