High-Dose Enalapril Treatment Reverses Myocardial Fibrosis in Experimental Uremic Cardiomyopathy
Open Access
- 27 January 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (1), e15287
- https://doi.org/10.1371/journal.pone.0015287
Abstract
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. 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. 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, p3 in SNX vs 5023±624 mm/mm3 in sham, p3) 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. The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular changes in SNX.Keywords
This publication has 50 references indexed in Scilit:
- Left Ventricular Geometry Predicts Cardiovascular Outcomes Associated with Anemia Correction in CKDJournal of the American Society of Nephrology, 2009
- Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood pressureKidney International, 2009
- Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidneyProceedings of the National Academy of Sciences of the United States of America, 2006
- Effect of celecoxib on experimental liver fibrosis in ratLiver International, 2005
- Cardiomyocyte loss in experimental renal failure: Prevention by ramiprilKidney International, 2003
- Effects of ACE inhibition and bradykinin antagonism on cardiovascular changes in uremic ratsKidney International, 2000
- To the EditorKidney International, 1999
- Angiotensin II Is Mitogenic for Cultured Rat Glomerular Endothelial CellsHypertension, 1996
- Vascular remodeling in systemic hypertensionThe American Journal of Cardiology, 1993
- Reduced capillary density in the myocardium of uremic rats—A stereological studyKidney International, 1992