Effect of vitamin E supplementation on cardiovascular function and structure in subtotal nephrectomized rats and on the progression of renal failure

ABSTRACT

Cardiovascular disease is the most common cause of premature death in patients with end stage renal disease, possibly due to a specific [uremic cardiomyopathy]. Furthermore, uremia is a state of increased oxidative stress. Thus, this study was designed to determine whether alpha-tocopherol [a known anti-oxidant] can interfere with the development of abnormal cardiovascullar function and structure in subtotal nephrectomized [STNx] rats, and whether it can modulate progression of renal failure after its supplementation to STNx rats. Thirty two male albino rats were subjected to partial renal ablation [subtotal nephrectomy; STNx], or to sham operation [n = 11]. STNx rats were either left untreated [n = 11], or received the antioxidant alpha-tocopherol at a dose of 200 mg/Kg body weight/day, orally [n = 10]. This study was terminated after 12 weeks from the renal ablation, blood pressure was measured, blood samples were collected for estimation of hemoglobin level, plasma malondialdehyde, creatinine and blood urea nitrogen levels. Then, followed by ischemia reperfusion of isolated hearts, the weights of whole heart and left ventricle were estimated. The hearts, kidneys, and aortae were subjected to histopathological examinations. Results of the present study showed significant elevation in blood pressure in untreated STNx group compared to treated STNx group, and to sham-operated group [149 +/- 7.6 versus 106 +/- 4.3 and 111 +/- 6.2 mmHg, respectively]. In vitro study of isolated hearts perfused in a Langendorff preparation showed a significant reduction in baseline peak tensions [PT] in untreated and treated STNx group compared to sham-operated group [9.5 +/- 0.9] and 10.4 +/- 1.2 versus 15.2 +/- 1.6 g. respectively]. Also, a significant prolongation of baseline time to peak tensions [TPT] in untreated and treated STNx group were, shown compared to sham-operated group [82 +/- 7.4 and 72 +/- 6.1 versus 40 +/- 3.0 msec, respectively]. In addition, untreated STNx group showed significant decrease in baseline myocardial flow rate in comparison to sham-operated group. After ischemia and reperfusion, heart rate [HR] recovery at 30 minute of reperfusion in untreated STNx group was worse than that in sham-operated group. As well peak developed tension, time to peak tension and myocardial flow rate recoveries at 30 minute of reperfusion in untreated STNx group were worse compared to sham operated group, and to treated STNx group. Biochemical studies confirmed that there were significant elevation in plasma malondialdehyde, creatinine and blood urea nitrogen levels in untreated STNx group compared to treated STNx group [5.5 +/- 0.38 versus 3.5 +/- 0.29 umol/L], [1.6 +/- 0.1 versus 0.7 +/- 0.05 mg/dl], [49.2 +/- 3.0 versus 26.3 +/- 1.7 mg/dl, respectively]. In addition, untreated STNx group showed significant reduction in hemoglobin level compared to treated STNx group and to sham-operated group [8.3 +/- 0.5 versus 10.4 +/- 0.8 and 11.9 +/- 0.3 g%, respectively]. Histopathological examinations showed glomerulosclerosis and thick basement membrane in remnant kidney models in untreated STNx group, also thick aortic intima with left ventricular hypertrophy were also observed in untreated STNx rats, events inhibited by vitamin E administration to STNx rats