Impairment of cardiac energy metabolism in vivo causes hemodynamic abnormality and increases cardiac expression of preproendothelin-1 mRNA

We investigated whether impairment of myocardial energy metabolism attenuat es cardiac function and increases cardiac endothelin-1 (ET-1) gene expressi on in rats. Three weeks after commencing administration of cobalt chloride (CoCl2), an inhibitor of mitochondrial function, the peak positive first de rivative of left ventricular (LV) pressure, an indicator of myocardial cont ractility, was significantly decreased in the CoCl2-treated rats. LV end-di astolic pressure and right ventricular systolic pressure were increased in the CoCl2-treated rats. Echocardiography showed that fractional shortening was significantly decreased in the CoCl2-treated rats. Myocardial expressio ns of acyl-CoA synthase mRNA, an enzyme involved in fatty acid utilization, was markedly decreased in the CoCl2-treated rats. Under such conditions, m yocardial expression of preproendothelin-1 mRNA and atrial natriuretic pept ide (ANP) mRNA, molecular markers of heart failure, was markedly increased in the CoCl2 rats. In conclusion, the data suggest that impairment of myoca rdial energy metabolism causes hemodynamic abnormality and increases molecu lar markers of heart failure (ET-1, ANP mRNA). These data suggest that myoc ardial energy metabolism is one of the factors involved in the upregulation of ET-1 gene expression in the failing heart.