Cell Biology – Immunology – Pathology
Kidney International (2003) 63, 1708–1713; doi:10.1046/j.1523-1755.2003.00927.x
Cardiomyocyte loss in experimental renal failure: Prevention by ramipril
Kerstin Amann, Karin Tyralla, Marie-Luise Gross, Ute Schwarz, Johannes Törnig, Christian Stefan Haas, Eberhard Ritz and Gerhard Mall
Department of Pathology, University of Erlangen, Erlangen, Germany; Department of Pathology, University of Heidelberg, Heidelberg, Germany; Department of Pathology, University of Darmstadt, Darmstadt, Germany; Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany; and Department of Internal Medicine, University of Erlangen, Erlangen, Germany
Correspondence: Dr. Kerstin Amann, Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. E-mail: kerstin.amann@patho.imed.uni-erlangen.de
Received 19 August 2002; Revised 14 November 2002; Accepted 2 January 2003.
Abstract
Cardiomyocyte loss in experimental renal failure: Prevention by ramipril.
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 
m3 vs. 10,067 2242 m3, P < 0.01) as well as a decrease of cardiomyocyte numbers per unit myocardial volume (61.2 16.2 vs. 92.2 20.9 
103/mm3) and per left ventricle (70.9 16.5 106 vs. 94.8 18.1 106, P < 0.05). Both abnormalities were abrogated by treatment with ramipril (6347 972.4 m3 and 106 18.9 103/mm3 or 118 39.5 106, 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.
Keywords:
renal failure, left ventricular hypertrophy, remodeling, apoptosis, ACE inhibitors
