INHIBITED EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR-I MESSENGER-RNA AND ATTENUATED CARDIAC-HYPERTROPHY IN VOLUME-OVERLOADED HEARTS TREATED WITH DIFLUOROMETHYLORNITHINE
P. Friberg et al., INHIBITED EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR-I MESSENGER-RNA AND ATTENUATED CARDIAC-HYPERTROPHY IN VOLUME-OVERLOADED HEARTS TREATED WITH DIFLUOROMETHYLORNITHINE, Growth hormone & IGF research, 8(2), 1998, pp. 159-165
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 p
roduction of polyamines. Volume overload was created in normotensive W
istar rats by means of an aorto-caval fistula. Difluoromethylornithine
(DFMO) 2%, which is a specific, irreversible blocker of ornithine dec
arboxylase, was administered in the drinking water to intervention gro
ups and one sham group, respectively, 24 h prior to surgery and for up
to 26 days. DFMO blocked transiently the early over-expression of rig
ht ventricular IGF-I mRNA and attenuated the rapid development of both
right and left ventricular hypertrophy during volume overload. Expres
sion of IGF-I mRNA in the right ventricle in the early phase of volume
overload appears to be dependent on activation of ornithine decarboxy
lase, whereas other pathways are involved in the later phase of cardia
c structural adaptation. Thus, these findings link together early and
late growth responses potentially important for compensatory cardiac h
ypertrophy. (C) 1998 Churchill Livingstone