The inhibitory mechanisms of amlodipine in human vascular smooth muscle cell proliferation

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is close ly related to vascular diseases. There is growing evidence that calcium ant agonists inhibit VSMC growth/proliferation, yet their molecular mechanisms remain to be determined. Recent reports suggest that p42/p44 mitogen-activa ted protein kinases (MAPKs) play an important role in cell growth and proli feration induced by growth factors. This study was designed to determine wh ether these MAPKs are involved in VSMC proliferation induced by basic fibro blast growth factor (bFGF) and to examine the inhibitory effect of amlodipi ne, Human VSMCs were obtained from inner mammary artery. p42/p44 MAPKs acti vity was measured by immunoblotting assay using anti-p42/p44 phospho-MAPK a ntibody, 1) bFGF (20 ng/ml) significantly activated p42/p44 MAPKs with a pe ak time of 5-15 min, which was maintained for 3 h. PD98059 (100 nM-10 mu M) , a specific inhibitor of MARK kinase, inhibited bFGF-induced p42/p44 MAPKs activation in a dose dependent manner. 2) Amlodipine (1-100 nM) dose-depen dently inhibited p42/p44 MAPKs activation by bFGF. 3) Amlodipine (10 nM) co uld inhibit both short-term and tong term p42/p44 MAPKs activation by bFGF, Our results indicate that bFGF could activate p42/p44 MAPKs, Amlodipine, w hich could inhibit bFGF-induced human VSMC proliferation, inhibited both sh ort-term and sustained p42/p44 MAPKs activation by bFGF, suggesting that bF GF-induced VSMC proliferation may be related to p42/p44 MAPKs activation, a nd that the antiproliferative effect of amlodipine may be related to its in hibition of p42/p44 MAPKs activation.