EFFECTS OF HYPOTHYROIDISM AND AORTIC CONSTRICTION ON MITOCHONDRIA DURING CARDIAC-HYPERTROPHY

We evaluated mitochondrial adaptations in the hearts of euthyroid and hypothyroid rats subject to aortic constriction for 2, 4, 7, 14, 21, a nd 28 d to induce a pressure-overload (PO), compared to sham-operated (SH) controls. PO animals attained higher arterial pressures than SH a nimals, by 55% in the euthyroid group, but only 14% in hypothyroid rat s after 28 d. The left ventricle/body weight ratio was increased 44% b y PO in the euthyroid group, and 26% in the hypothyroid group. PO atte nuated the decline in cardiac growth in the hypothyroid group. Thus, h ypothyroidism reduces the magnitude of the PO, but not the potential f or hypertrophy in response to PO. Cytochrome c oxidase activity (CYTOX ) was unchanged by PO in the euthyroid animals, indicating that the sy nthesis of mitochondria paralleled adaptive growth. However, CYTOX act ivity decreased up to 20% in the hypothyroid groups (P < 0.05) and was unaltered by PO. Thus, PO prevented the decline in growth, but not th e decline in mitochondrial enzymes due to hypothyroidism. The lack of effect of PO on mitochondria was partly due to pretranslational change s, since CYTOX subunit VIc mRNA was reduced by PO in the hypothyroid a nimals, but not in the euthyroid group. Levels of the chaperones HSP60 and GRP75, as well as HSP60 mRNA were unaffected by hypothyroidism, b ut paralleled adaptive growth induced by PO. Hypothyroidism changes th e pattern of gene expression within the heart leading to altered mitoc hondrial composition. This cannot be compensated for by conditions of increased physiological demand.