THE RESPONSE OF NORMAL HUMAN SMOOTH MUSCLE CELLS TO PLATELET-DERIVED GROWTH FACTOR-AA (PDGF-AA) IS INHIBITED BY NIFEDIPINE. † 1286

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We have previously found that platelet-derived growth factor-AA (PDGF-AA) is elevated in fetal vascular smooth muscle cells (VSMC) of preeclamptic placentas. This growth factor might account in part for the excessive growth of VSMC noted in these vessels. Calcium entry is a prerequisite for the induction of DNA synthesis by PDGF-AA. Therefore, we propose that nifedipine, a Ca2+channel blocker, might inhibit the response of human aortic VSMC(CRL-1999, American Type Culture Collection) to PDGF-AA. VSMC were grown in F12K medium with 5% fetal bovine serum to near confluence in 96-well plates. Cells were preincubated for 20 hours with or without nifedipine and were further stimulated by the addition of 5 ng/ml PDGF-AA. Twenty-four hours later, 3H-thymidine was incorporated into the cells during a pulse of 15 hours. The addition of PDGF-AA significantly increased the proliferation of VSMC over baseline (7770 ±240 SEM vs. 4780 ±90 SEM, p<0.0001). The contribution of PDGF-AA to the basal growth of the VSMC was shown to be negligible, since the addition of monoclonal antibody to the a-receptor for PDGF-AA did not affect the growth in medium alone. On the other hand, the same antibody blocked the additive response to PDGF-AA. Furthermore, nifedipine inhibited the response to PDGF-AA in a dose-dependent manner(r=-0.87, p<0.01), exerting a maximum inhibitory effect at 500 nM. These results suggest 1) nifedipine appears to block the PDGF-AA stimulated growth of VSMC in vitro; 2) pharmacological intervention by nifedipine administration might reduce excessive VSMC growth and improve fetal-placental blood flow in preeclampsia. The physiological relevance of these findings will be tested in animals.

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(Spon by: Edwin G Brown, MD)

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