Effect of antioxidant therapy with dl-α-tocopherol on cardiovascular structure in experimental renal failure

Abstract

Background. Chronic renal failure is characterized by remodeling of the structure of the heart and the vasculature, for example, left ventricular hypertrophy, myocardial fibrosis, capillary/myocyte mismatch, as well as thickening of intramyocardial arteries and of peripheral arteries and veins. Furthermore, uremia is a state of increased oxygen stress. It was the purpose of this study to examine whether these findings are interrelated. Methods. To investigate whether antioxidative therapy with dl-α-tocopherol (Toco; vitamin E) interferes with the development of abnormal cardiovascular structure in experimental renal failure, 28 male Sprague-Dawley rats were subjected to partial renal ablation (subtotal nephrectomy, SNX) or to sham operation (sham). SNX were either left untreated or received the antioxidant Toco (2 × 1500 IE/kg BW/week in the pellets). Blood pressure was measured using tail plethysmography. The experiment was terminated after 12 weeks. Heart and left ventricular weight were determined and the following parameters were measured using morphometry and stereology: volume densities of cardiomyocytes, capillaries and non-vascular interstitium; length density and total length of cardiac capillaries, wall thickness of intramyocardial arterioles and of the aorta. Results. Systolic blood pressure and body weight were comparable in all groups. Treatment with Toco led to significantly increased plasma concentrations of Toco. Left ventricular weight and wall thickness of intramyocardial arteries were significantly higher in both SNX groups compared to sham controls. Volume density of the cardiac interstitial tissue was significantly higher in untreated SNX than in Toco treated SNX and sham control rats. Length density of capillaries was significantly lower in untreated SNX than in control rats; however, the values were significantly higher, and even higher than in sham controls, when SNX were treated with Toco. Conclusions. Treatment with the antioxidant dl-α-tocopherol prevented cardiomyocyte/capillary mismatch, and to some extent also myocardial fibrosis in rats with renal failure. The results point to a role of oxidative stress in the genesis of myocardial interstitial fibrosis and capillary deficit of the heart.