Cardiomyocyte loss in experimental renal failure: prevention by ramipril

Kidney Int. 2003 May;63(5):1708-13. doi: 10.1046/j.1523-1755.2003.00927.x.


Background: The development of left ventricular hypertrophy (LVH) and of structural abnormalities of the heart is a key abnormality in renal failure that potentially contributes to the high rate of cardiac death. In renal failure, the behavior of cardiomyocyte volume and number in the development of LVH has so far not been investigated. A potential role of the (local) renin-angiotensin system (RAS) in the genesis of LVH has been suspected. It was the aim of the present study in short-term experimental renal failure (1) to characterize cardiomyocyte volume and number and (2) to study whether they are affected by the angiotensin-converting enzyme (ACE) inhibitor ramipril.

Methods: Sprague-Dawley rats (N = 8 to 10 per group) had a subtotal nephrectomy (SNX) or sham operation and followed for 8 weeks. One SNX group received the ACE inhibitor ramipril (0.5 mg/kg body weight) in the drinking fluid. After perfusion fixation, the morphology of the heart was investigated using stereologic techniques.

Results: Systolic blood pressure was slightly, but not significantly, higher in untreated SNX, but the left ventricular (LV) weight and LV weight/body weight ratio (2.32 +/- 0.20 mg/g) were significantly higher in SNX than in sham-operated animals (1.90 +/- 0.16 mg/g). Sarcomeric length was not significantly different between SNX and sham-operated animals. There was an increase in the number of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL)-positive myocytes in SNX compared to sham-operated animals and a significant increase in cardiomyocyte volume (15,713 +/- 4557 microm3 vs. 10,067 +/- 2242 microm3, P < 0.01) as well as a decrease of cardiomyocyte numbers per unit myocardial volume (61.2 +/- 16.2 vs. 92.2 +/- 20.9 x 103/mm3) and per left ventricle (70.9 +/- 16.5 x 106 vs. 94.8 +/- 18.1 x 106, P < 0.05). Both abnormalities were abrogated by treatment with ramipril (6347 +/- 972.4 microm3 and 106 +/- 18.9 103/mm3 or 118 +/- 39.5 x 106, respectively), which also completely prevented the increase in LV weight/body weight ratio (1.83 +/- 0.14 mg/g).

Conclusion: LVH in renal failure is characterized by cardiomyocyte hypertrophy, but also cardiomyocyte drop out. A role of the RAS is suggested by the beneficial effect of ramipril treatment that is not accounted for by differences in blood pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Disease Models, Animal
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / pathology*
  • Hypertrophy, Left Ventricular / prevention & control*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Myocytes, Cardiac / pathology
  • Ramipril / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / complications*
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Sarcomeres / pathology


  • Angiotensin-Converting Enzyme Inhibitors
  • Ramipril