Development of heart failure following isoproterenol administration in the rat: Role of the renin-angiotensin system

Daniela Grimm, Dietmar Elsner, Heribert Schunkert, Michael Pfeifer, Daniel Griese, Günter Bruckschlegel, Frank Muders, Günter A.J. Riegger, Eckhard P. Kromer

Research output: Contribution to journalArticlepeer-review

213 Scopus citations


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.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalCardiovascular Research
Issue number1
StatePublished - Jan 1998
Externally publishedYes


  • Angiotensin converting enzyme inhibition
  • Catecholamine
  • Extracellular matrix proteins
  • Heart failure
  • Myocardium


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