EFFECT OF CALCIUM-ANTAGONISTS ON RNA-SYNTHESIS OF NIH-3T3 CELLS

Calcium antagonists have been shown to induce a decrease in peripheral vascular resistance as well as a decrease in synthesis of vascular-wa ll matrix proteins. It has been shown previously that calcium antagoni sts decrease RNA synthesis of cultured, vascular, smooth-muscle cells. Here, these findings are extended to the investigation of whether cal cium antagonists produce their vascular effects through their action o n vascular, smooth-muscle cells only or whether they regulate fibrobla st cells as well. It is demonstrated that in a concentration-dependent manner verapamil, diltiazem, and nifedipine each induced a decrease i n RNA synthesis of quiescent and serum-stimulated NIH 3T3 cells, a fib roblast cell line shown to express voltage-dependent Ca2+ channels. Ve rapamil and nifedipine (10(-5)M) and diltiazem (10(-4)M) caused a mark ed decrease of basal and serum-induced increase in [H-3]uridine uptake of NIH 3T3 cells. This is the first report to demonstrate that calciu m antagonists have a direct effect on a fibroblast cell line leading t o a decrease of RNA synthesis. Such findings suggest that calcium-anta gonist vascular effects extend beyond vascular smooth muscle cells to connective tissues associated with extracellular-matrix protein produc tion.