Angiotensin II stimulates gene expression of cardiac insulin-like growth factor I and its receptor through effects on blood pressure and food intake

Angiotensin II (Ang II) is known to act as a growth factor and may be invol ved in cardiac remodeling. We have shown that insulin-like growth factor-I (IGF-I) is an autocrine mediator of growth responses to Ang II in vascular smooth muscle cells in vitro, and we hypothesized that IGF-I also serves as an important modulator of cardiovascular growth in vivo. To study the effe ct of Ang II on cardiac IGF-I, we infused rats for 3, 7, or 14 days with An g II through osmotic minipumps. After 7 days, left ventricular mass normali zed for body weight was increased by 20% (P<0.01) in Ang II rats compared w ith pair-fed control rats that were given a restricted amount of food ident ical to that eaten by the anorexic, Ang II-infused rats. Ang II increased l eft ventricular IGF-I mRNA levels by 1.5- to 1.8-fold compared with ad libi tum-fed or pair-fed control rats (P<0.05). Cardiac IGF-I protein was increa sed correspondingly and was localized on the cardiomyocytes. Treatment with hydralazine abolished the induction of IGF-I mRNA, which indicates that An g II induces cardiac IGF-I mRNA expression through a pressor-mediated mecha nism. IGF-I receptor (IGF-IR) mRNA was induced 2.1-fold in Ang II rats comp ared with ad libitum-fed rats (P<0.01). However, this increase was also obs erved in pair-fed controls and is thus due to the anorexigenic effect of An g II. We have recently shown that circulating IGF-I levels are reduced in r esponse to Ang II infusion. Elevation of IGF-I levels by coinfusion of IGF- I and Ang II significantly increased left ventricular index by 16% compared with rats infused with Ang II alone (P<0.05). In conclusion, autocrine upr egulation of cardiac IGF-I and IGF-IR mRNA by Ang II occurs through hemodyn amic and nonhemodynamic mechanisms, respectively, and may modulate cardiac structural changes that occur in hypertension.