Ornithine Decarboxylase in Cardiac Hypertrophy in the Rat

Abstract

Ornithine decarboxylase, a possible rate-limiting enzyme in the synthesis of polyamines, was assayed in hearts of normal rats, sham-operated rats, and rats subjected to aortic constriction. In the hearts of rats with constricted aortas, significantly increased enzyme activity compared with that in the hearts of sham-operated rats was observed 2, 4, 6, and 8 hours and 3, 5, and 10 days after operation, and two peaks in activity occurred--one at 4 hours and the other at 5-10 days. Increased ornithine decarboxylase activity was one of the earliest changes associated with cardiac hypertrophy. The changes in enzyme activity correlated well with the subsequent hypertrophy in the hearts of rats with aortic constriction and with the regression in the hearts of sham-operated rats, suggesting a role for polyamines in the regulation of cardiac growth. The early increase in ornithine decarboxylase activity in hearts of rats with aortic constriction was inhibited by actinomycin D, 8-azaguanine, and cycloheximide, indicating that RNA and protein synthesis are involved in the process. Actinomycin D given 30 minutes after operation or even at the time of aortic constriction failed to inhibit the increase in the enzyme activity, suggesting that the transcription required for the increase occurs early after operation. Cycloheximide given 1 hour before the rats were killed markedly decreased the enzyme activity, and the estimated half-life of cardiac ornithine decarboxylase was comparable to that of the reported short-lived liver ornithine decarboxylase. The study suggests that the synthesis of ornithine decarboxylase is influenced at the stage of transcription by mechanical stress on the myocardium and that polyamines might have a regulatory role in cardiac hypertrophy and regression.