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Am J Physiol Heart Circ Physiol 274: H1742-H1748, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 5, H1742-H1748, May 1998

PDGF-BB-induced DNA synthesis is delayed by angiotensin II in vascular smooth muscle cells

Gunilla Dahlfors1, Yun Chen1, Maria Wasteson1, and Hans J. Arnqvist2

Departments of 1 Cell Biology and 2 Internal Medicine, Faculty of Health Science, University of Linköping, S-58185 Linköping, Sweden

The interaction of ANG II with platelet-derived growth factor (PDGF)-BB-induced DNA synthesis was studied in cultured rat aortic smooth muscle cells. PDGF-BB-induced DNA synthesis was delayed (~6-8 h) by ANG II as shown by a time-course experiment. Losartan, an AT1-receptor antagonist, blocked the transient inhibitory effect of ANG II, whereas the AT2-receptor antagonist PD-123319 had no effect. Autocrine- or paracrine-acting transforming growth factor-beta 1 (TGF-beta 1), believed to be a mediator of ANG II-induced inhibitory effects, was not responsible for the delay of PDGF-BB-induced DNA synthesis, because a potent TGF-beta 1 neutralizing antibody could not reverse this effect of ANG II, nor was the delay of the PDGF-BB effect caused by inhibition of PDGF-beta -receptor phosphorylation as shown by Western blot analysis of immunoprecipitated PDGF-beta receptor. In conclusion, our results show that ANG II can exert a transient inhibitory effect on PDGF-BB-induced proliferation via the AT1 receptor.

rat; angiotensin AT1 receptor; transforming growth factor-beta 1


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