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- Title
Complete Regression of Myocardial Fibrosis after High Dose Enalapril Treatment in Experimental Renal Failure.
- Authors
Tyralla, K.; Adamczak, M.; Gross, M. L.; Koch, A.; Ritz, E.; Amann, K.
- Abstract
Objective: Patients with renal failure develop very early cardiovascular alterations like left ventricular hypertrophy (LVH), myocardial fibrosis and thickening of intra- and extracardiac vessels. These structural abnormalities are held responsible for the much higher rate of cardiac death in uremic patients, compared to the general population. Interventions blocking the renin angiotensin system have been shown to interfere with the development of these cardiovascular structural alterations. Until now it is unclear to what extent these agents can also reverse existing LVH and associated cardiovascular changes. The aim of the study was to investigate the effect of high dose enalapril treatment on existing cardiovascular alterations in experimental renal failure. Methods: 73 male Sprague Dawley rats were either subtotally nephrectomized (SNX) or sham operated (sham). 8 weeks after surgery they were sacrificed by perfusion fixation or allotted to three arms: treatment with enalapril (E; 48 mg/kg/d) or solvent or furosemide + dihydralazine (F + D) for four weeks. The morphology of the heart and the aorta was evaluated using morphometrical and stereological techniques. 73 male Sprague Dawley rats were either subtotally nephrectomized (SNX) or sham operated (sham). 8 weeks after surgery they were sacrificed by perfusion fixation or allotted to three arms: treatment with enalapril (E; 48 mg/kg/d) or solvent or furosemide + dihydralazine (F + D) for four weeks. The morphology of the heart and the aorta was evaluated using morphometrical and stereological techniques. Results: Systolic blood pressure, albumine excretion, absolute and relative left ventricular weight were significantly higher in SNX compared to sham and were significantly reduced after E treatment whereas F + D had no effect. 12 weeks after SNX a significantly higher volume density of interstitial tissue (2.57 ± 0.43% in SNX vs 1.5 ± 0.43% in sham) and a somewhat lower capillarisation in the myocardium was found. E treatment led to complete regression of myocardial fibrosis (1.6 ± 0.25%), but not of capillary rarefaction in SNX. In contrast F + D treatment showed no effect on fibrosis or reduced capillarisation. The aorta and small intramyocardial arterioles of SNX animals were caracterized by a significantly increased media thickness and dissaray of elastic fibers when compared to sham. Treatment with the ACE inhibitor E led to a slight, but uncomplete regression of these alterations. Conclusions: The study indicates that high dose enalapril treatment in experimental renal failure induces complete regression of LVH and myocardial fibrosis, but not of capillarisation of the myocardium and vascular alterations.
- Subjects
DISEASE complications; KIDNEY diseases; FIBROSIS; CARDIAC surgery &; psychology; BLOOD circulation; FUROSEMIDE
- Publication
Kidney & Blood Pressure Research, 2004, Vol 27, Issue 5/6, p292
- ISSN
1420-4096
- Publication type
Article