Lipid peroxidation and myocardial vulnerability in hypertrophied SHR myocardium

In a comparison using age-matched Wistar-Kyoto rats (WKY), 16-week-old male spontaneously hypertensive rat (SHR) hearts were examined histologically and biochemically on the first and fourth day after administration of 20 mg/kg doxorubicin in order to examine whether membrane abnormalities in hypertrophied SHR myocardium are caused by lipid peroxidation. Morphological examination of the SHR revealed focal myocytolysis on the first day and severe cardiomyopathy involving diffuse myocytolysis and vacuolar degeneration in the left ventricle on the fourth day. The activity of a membrane-related enzyme, Na+/K(+)-ATPase, was already lower in control SHR than that of control WKY and was lower in both SHR and WKY than in the respective saline groups on the first day after administration, whereas the enzyme activity in the doxorubicin-treated SHR was not significantly different from that of the treated WKY. A thiobarbituric acid-reactant substance, a lipid peroxidation marker, was significantly higher in treated SHR than it was in the treated WKY on the first day. Furthermore, in comparison with WKY, alpha-tocopherol in the left ventricle in SHR was significantly lower on the fourth day after administration. These results show that a proneness to lipid peroxidation in the membrane system is closely associated with severity of doxorubicin-induced cardiomyopathy in SHR and suggests that membrane lipid peroxidation may cause a higher degree of vulnerability in hypertrophied SHR myocardium.