EFFECTS OF IGF-I ON CARDIAC GROWTH AND EXPRESSION OF MESSENGER-RNAS CODING FOR CARDIAC PROTEINS AFTER INDUCTION OF HEART HYPERTROPHY IN THERAT

Adult rat cardiomyocytes in long-term culture reexpress several fetal cardiac proteins which also reappear during overload heart hypertrophy in vivo. IGF-I decreases reexpression of some of these proteins and s timulates myofibrillogenesis. IGF-I might therefore contribute to enha ncing readaptation of the heart to overload. In order to test this hyp othesis, hypertension was induced in male Wistar Kyoto rats by constri ction of the left renal artery and an infusion of 500 mu g/day of reco mbinant human IGF-I (rhIGF-I) or vehicle was started after the operati on via intraabdominally implanted osmotic minipumps, In the vehicle-tr eated hypertensive animals body weight gain was reduced after 3, 7 and 14 days, whereas rhIGF-I-treated hypertensive animals continued to ga in weight like sham-operated animals. Left ventricular weight and the left, but not the right ventricle/body weight ratio increased more in rhIGF-I- than in vehicle-infused rats. Left ventricular IGF-I mRNA lev els remained unchanged after renal clipping in both vehicle- and rhIGF -I-treated rats. However, beta-myosin heavy chain (MHC) mRNA in the le ft ventricle was 6- to 10-fold increased in clipped controls during th e whole postoperative period, and rhIGF-I reduced this increase by mor e than 50% on days 7 and 14. On the first postoperative day rhIGF-I pr evented the decrease (50%) of alpha-MHC mRNA and the increase (2.5-fol d) of atrial natriuretic factor mRNA in the left ventricle. Renal clip ping did not alter cardiac alpha-actin, but enhanced skeletal alpha-ac tin mRNA expression in the left ventricle up to 2.5-fold. However, bot h mRNAs were unaffected by rhIGF-I treatment. Restoration of body weig ht gain and stimulation of left ventricular cardiac weight by rhIGF-I as well as partial reversion of hypertension-induced changes in cardia c protein expression may reflect beneficial effects contributing to en hance readaptation of the heart to overload.