Aims: Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death.\nBlockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what\nextent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose\nenalapril treatment on these alterations.\nMethods: Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight\nweeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of\nfurosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological\ntechniques and TaqMan PCR.\nResults: After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly\nhigher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac\ninterstitial tissue (2.5760.43% in SNX vs 1.5060.43% in sham, p,0.05) and a significantly lower capillary length density\n(45326355 mm/mm3 in SNX vs 50236624 mm/mm3 in sham, p,0.05) were found. Treatment of SNX with enalapril from\nweek 8ââ?¬â??12 significantly improved myocardial fibrosis (1.6360.25%, p,0.05), but not capillary reduction (39086486 mm/\nmm3) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect.\nSignificantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of\nelastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause\ncomplete regression of these alterations.\nConclusions: The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular\nchanges in SNX.
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