CARDIAC CATECHOLAMINE METABOLISM IN COPPER-DEFICIENT RATS

After parturition, Sprague-Dawley dams were fed diets containing either 0.6 (-Cu) or 6 (+Cu) mg of copper/kg of diet. Pups were weaned either to the diet of their dam or to the diet fed to dams in the other treatment group in a crossover design. At 7 wk of age, Cu-deficient rats were characterized by low tissue Cu and an enlarged heart with increased levels of dopamine (DA) and decreased levels of norepinephrine (NE). These changes resulting from Cu deficiency were independent of gender. In vivo synthesis of cardiac NE from DA in Cu-adequate rats was significantly greater than in Cu-deficient rats. Turnover of cardiac NE was estimated from the temporal change in the specific activity of [H-3]NE. Fractional turnover rates (percentage per hour) of cardiac NE were similar in both dietary groups, although the cardiac turnover of NE (nanograms per hour) was 1.4-fold higher in Cu-adequate rats than in Cu-deficient rats. Repletion of Cu-deficient rats with dietary Cu increased the total amount of cardiac NE to 78 and 93% of control values after 1 and 2 d, respectively. Significant changes in the quantities of NE and DA in the heart of rats whose intake of Cu was restricted from birth were first detected at 4 wk of age, but cardiac hypertrophy was not observed until 5 wk of age. The data support the proposal that the altered levels of DA and NE in the heart of Cu-deficient rats are primarily the result of decreased activity of DA-B-monooxygenase and demonstrate that Cu supplementation rapidly repletes cardiac NE in Cu-deficient rats. Moreover, changes in the concentrations of NE and DA in the heart precede and may contribute to the development of cardiac hypertrophy.