Atria and Ventricles of Copper-Deficient Rats Exhibit Similar Hypertrophy and Similar Altered Biochemical Characteristics

Abstract

Abstract

Male Holtzman rats were offered a semipurified low-copper (Cu) diet (0.36 mg Cu/kg) for 5-6 weeks to further characterize cardiac hypertrophy, which accompanies Cu deficiency. Cu-adequate (controls) were given supplemental Cu (20 μg/ml) in their drinking water, and Cu-deficient rats were given deionized water. Cu-deficient rats had lower plasma ceruloplasmin activity, lower hemoglobin levels, higher heart weights, and similar body weights compared with Cu-adequate rats. The relative degree of hypertrophy in the right ventricle of Cu-deficient rats was significantly higher (2.3-fold) than that in the left ventricle and atria (both were 1.9-fold higher than the values in Cu-adequate rats). Edema was not detected. Ventricles and atria of Cudeficient rats had markedly lower Cu and no significant differences in iron concentrations compared with Cu-adequate rats. Heart protein concentrations were not altered consistently by Cu deficiency. Enzyme activities of the cuproenzymes cytochrome-c oxidase (CCO), copper, zinc-superoxide dismutase (SOD), dopamine β-monooxygenase (DBM), peptidylglycine β-amidating monooxygenase (PAM), and the selenoenzyme glutathione peroxidase (GPX) were measured in the atria and ventricles. Cu deficiency resulted in lower specific activities of all cuproenzymes, with the exception of ventricular PAM. GPX was not altered by chamber region or diet. Specific activity of PAM was 200-fold higher in atria than in ventricles in control rats. Catecholamine analyses by HPLC confirmed that, like ventricular tissue, atria of Cudeficient rats had lower norepinephrine and higher dopamine concentrations, consistent with lower DBM activity. Another experiment detected no differences between the two dietary groups in mean arterial blood pressure, heart rates, or responses after challenge with angiotensin II, phenylepherine, or acetylcholine in cannulated rats. In this Cu-deficient rat model, all chambers of the heart exhibit similar and marked hypertrophy. Biochemical alterations following dietary Cu deficiency were also similar in atria and ventricles. The hypertrophic response appears different from the response to simple pressure or volume overload.