Inhibited expression of insulin-like growth factor I mRNA and attenuated cardiac hypertrophy in volume overloaded hearts treated with difluoromethylornithine.

The present study examined whether the previously reported hypertrophy and increased expression of insulin-like growth factor I (IGF-I) mRNA in the volume-overloaded right ventricle was dependent on an intact production of polyamines. Volume overload was created in normotensive Wistar rats by means of an aorto-caval fistula. Difluoromethylornithine (DFMO) 2%, which is a specific, irreversible blocker of ornithine decarboxylase, was administered in the drinking water to intervention groups and one sham group, respectively, 24 h prior to surgery and for up to 26 days. DFMO blocked transiently the early over-expression of right ventricular IGF-I mRNA and attenuated the rapid development of both right and left ventricular hypertrophy during volume overload. Expression of IGF-I mRNA in the right ventricle in the early phase of volume overload appears to be dependent on activation of ornithine decarboxylase, whereas other pathways are involved in the later phase of cardiac structural adaptation. Thus, these findings link together early and late growth responses potentially important for compensatory cardiac hypertrophy.