title: High-dose enalapril treatment reverses myocardial fibrosis in experimental uremic cardiomyopathy.
abstract: OBJECTIVE
  Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death. Blockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what extent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose enalapril treatment on these alterations.
  
  
  METHODS
  Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight weeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of furosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological techniques and TaqMan PCR.
  
  
  RESULTS
  After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly higher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac interstitial tissue (2.57±0.43% in SNX vs 1.50±0.43% in sham, p<0.05) and a significantly lower capillary length density (4532±355 mm/mm(3) in SNX vs 5023±624 mm/mm(3) in sham, p<0.05) were found. Treatment of SNX with enalapril from week 8-12 significantly improved myocardial fibrosis (1.63±0.25%, p<0.05), but not capillary reduction (3908±486 mm/mm(3)) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect. Significantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of elastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause complete regression of these alterations.
  
  
  CONCLUSIONS
  The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular changes in SNX.
authors.affiliation: Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Tyralla
authors.forename: Marcin
authors.initials: M
authors.lastname: Adamczak
authors.forename: Kerstin
authors.initials: K
authors.lastname: Benz
authors.forename: Valentina
authors.initials: V
authors.lastname: Campean
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Gross
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004656:Enalapril / Q000008:administration & dosage*; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014511:Uremia / Q000150:complications*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril