Interaction of angiotensin II and the insulin-like growth factor system in vascular smooth muscle cells

We studied the effects and interactions of ANG II and the insulin-like growth factor (IGF) system in cultured rat aortic smooth muscle cells. ANG II (1 microM) and IGF-I (10 nM) stimulated both DNA and protein synthesis. The effects of the two peptides in combination were additive or more than additive. The AT(1) receptor antagonist losartan (10 and 100 microM) blocked their synergistic effect on DNA synthesis. IGF binding protein (IGFBP)-1 inhibited the effect of IGF-I but not that of ANG II on DNA synthesis. IGF-I stimulated gene expression of IGFBP-2 and IGFBP-4. ANG II decreased IGF-I, IGFBP-2, and IGFBP-4 transcripts but increased the IGF-I receptor transcript. IGF-I and ANG II in combination had similar effects on gene expression as ANG II alone. The IGFBP-2 and IGFBP-4 peptides could be detected in the conditioned medium. Our results show that ANG II and IGF-I have synergistic effects on vascular smooth muscle cells and that they interact in several ways.