Role of polyamines in isoproterenol-induced cardiac hypertrophy: effects of alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase

DFMO is a selective irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the polyamine biosynthetic pathway. DFMO was utilized to determine the role of polyamines in isoproterenol (ISO)-induced cardiac hypertrophy. Daily subcutaneous administration of 200 mg/kg of DFMO reduced cardiac putrescine levels but did not significantly alter the basal levels of spermidine or spermine, nor was normal cardiac growth affected. ISO-induced cardiac hypertrophy was accompanied by increased putrescine and spermidine levels but spermine was not significantly altered. DFMO reversed the ISO-induced increases in putrescine and inhibited or attenuated both the increases in spermidine content and the cardiac hypertrophy. Although normal ODC activity appears not to be necessary for the maintenance of basal levels of polyamines or for normal cardiac growth, sustained inhibition of ODC interferes with ISO-induced elevations of putrescine, spermidine and heart weight.