THE MECHANISMS OF INHIBITION OF AMLODIPINE ON HUMAN VASCULAR SMOOTH MUSCLE CELL PROLIFERATION

AIM　Mitogen-activated protein kinase (MAPK) plays an important role on growth factor-induced cell growth and proliferation. This study was designed to determine whether MAPK is involved in the inhibitory effect of amlodipine on basic fibroblast growth factor (bFGF)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS　Human VSMC were obtained from lower mammary artery. MAPK activity was measured by immunobloting using anti-p42/p44 phospho-MAPK antibody. RESULTS　bFGF (20 ng.mL^-1) significantly activated MAPK with a peak time at 5～15 min, maintained for 3 h. PD98059 (0.1～10 μmol.L^-1), a specific inhibitor of MAPK kinase, inhibited bFGF-induced MAPK activation in a dose-dependent manner. Amlodipine (1～100 nmol.L^-1) dose-dependently inhibited MAPK activation by bFGF. Amlodipine (10 nmol.L^-1) was shown to inhibit both short-term and long-term MAPK activation induced by bFGF. CONCLUSION　The results indicated that bFGF could significantly activate MAPK. Amlodipine, which could inhibit bFGF-induced human VSMC proliferation, inhibit both short-term and sustained MAPK activation by bFGF. It is suggested that bFGF-induced VSMC proliferation may be related to MAPK activation, and the antiproliferation effect of amlodipine may be related to its inhibition of MAPK activation.