Effects of Inhibition of Angiotensin-Converting Enzyme on Myocardial and Myocyte Remodeling in Chronic Volume Overload-Induced Cardiac Hypertrophy in the Dog

  • Sanford P. Bishop
  • Louis J. Dell’Italia
Part of the Progress in Experimental Cardiology book series (PREC, volume 2)


The data from our studies with chronic mitral regurgitation (MR) in the dog demonstrate that the ventricular and myocyte remodeling in this model, characterized by ventricular dilation and myocyte elongation, are not returned toward normal by treatment with the converting enzyme inhibitor, ramipril. However, in spite of this failure to reduce cardiac hypertrophy or to prevent the remodeling associated with this model of chronic volume overload, there was functional improvement in the animals, as determined by the lower left ventricular filling pressures and pulmonary artery pressures in the treated animals compared with the controls. Ramipril also returned myocardial Ang II levels to control level. This suggests that there may have been a regulatory mechanism on contractile function acting through this chemical mediator.

Our results suggest that diastolic wall stress activates the cardiac renin-angiotensin system (RAS) and that angiotensin (Ang) II and angiotensin-converting enzyme (ACE) may play a functional role in the eccentric pattern of hypertrophy observed in the volume overload model of MR in the dog heart. Additional future studies are needed to further characterize the relative roles of ACE and chymase in Ang II formation in this model that is relevantly important to the human heart. MR produces an increase in intracardiac Ang II without the interstitial fibrosis that has been found in pressure overload. This finding is of particular interest because the heart is a target organ for Ang II, a growth factor for myocytes and fibroblasts [1–5], which has also been associated with myocyte necrosis [6]. Thus, the mechanisms by which the RAS may mediate eccentric hypertrophy in the low pressure volume overload of MR is open to question. The beneficial effect of converting enzyme inhibitor on myocardial function in this model of volume overload, but in the absence of morphological improvement, remains speculative but may be related to alterations in the RAS in the cardiac muscle produced by the treatment.


Right Ventricular Mitral Regurgitation Cardiac Hypertrophy Volume Overload Pressure Overload 
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Sanford P. Bishop
    • 1
  • Louis J. Dell’Italia
    • 1
  1. 1.Departments of Pathology and MedicineThe University of Alabama at BirminghamBirminghamUSA

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