VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION IN SHR AND WKY RATS - EVIDENCE FOR SPECIFIC DIFFERENCES IN GROWTH-INHIBITORY REGULATORY MECHANISMS

1. This study examined and compared the actions of transforming growth factor-beta1 (TGF-beta1), heparin, dexamethasone and interferon-gamma on platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferati on of vascular smooth muscle cells (VSMC) from normotensive, Wistar-Ky oto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Heparin, dexamethasone and interferon-gamma all inhibited VSMC proliferation st imulated by PDGF-BB in both SHR and WKY rats. There was no difference (P>0.05) in their inhibitory effects, which varied between 40 and 85% for the different agents. 3. Similarly, TGF-beta1 inhibited PDGF-BB-st imulated VSMC proliferation in WKY rats by approximately 50%. In contr ast, TGF-beta1 potentiated growth factor action on cell proliferation in the SHR by approximately 40%. 4. Specific TGF-beta1-stimulated regu latory mechanisms involved in the inhibition of proliferation are abse nt in SHR and this defect may contribute to the vascular hypertrophy w hich is apparent in genetic hypertension.