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

We studied the effects and interactions of ANG II and the insulin-like grow th factor (IGF) system in cultured rat aortic smooth muscle cells. ANG II ( 1 mu M) and IGF-I (10 nM) stimulated both DNA and protein synthesis. The ef fects of the two peptides in combination were additive or more than additiv e. The AT(1) receptor antagonist losartan (10 and 100 mu M) blocked their s ynergistic 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 stimula ted 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 I I alone. The IGFBP-2 and IGFBP-4 peptides could be detected in the conditio ned 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.