EFFECT OF CALCIUM-CHANNEL BLOCKERS ON THE GROWTH OF HUMAN VASCULAR SMOOTH-MUSCLE CELLS DERIVED FROM SAPHENOUS-VEIN AND VASCULAR GRAFT STENOSES

Vascular restenosis after invasive interventions is an important clini cal problem for which no preventive pharmacologic therapy exists. Calc ium channel blockers have been shown to inhibit myointimal hyperplasia in animal models of restenosis and in some small and flawed clinical coronary restenosis trials. We examined the inhibitory effect of amlod ipine, verapamil, and diltiazem on the growth of cultured human vascul ar smooth muscle cells (VSMC) derived from saphenous vein (n = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl H- 3]thymidine uptake studies. Amlodipine and verapamil produced signific ant inhibition (30%) of VSMC proliferation and DNA synthesis at 10 mu M but not at 500 nM-1 mu M. To our knowledge, this is the first study to examine the antiproliferative effect of calcium channel blockers in VSMC derived from human graft stenoses. Growth inhibition of VSMC fro m graft stenoses was not significantly different from that of control saphenous vein-derived cells. We conclude, therefore, that calcium cha nnel blockers inhibit human VSMC proliferation in vitro, regardless of whether the cells were grown from graft stenoses or saphenous vein. H owever, the concentrations at which these calcium channel blockers eli cit antiproliferative effects may not be attainable during therapeutic dosing in humans.