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-wall matrix proteins. It has been shown previously that calcium antagonists decrease RNA synthesis of cultured, vascular, smooth-muscle cells. Here, these findings are extended to the investigation of whether calcium antagonists produce their vascular effects through their action on vascular, smooth-muscle cells only or whether they regulate fibroblast cells as well. It is demonstrated that in a concentration-dependent manner verapamil, diltiazem, and nifedipine each induced a decrease in RNA synthesis of quiescent and serum-stimulated NIH 3T3 cells, a fibroblast cell line shown to express voltage-dependent Ca²⁺ channels. Verapamil and nifedipine (10^-5 M) and diltiazem (10^-4 M) caused a marked decrease of basal and serum- induced increase in [³H]uridine uptake of NIH 3T3 cells. This is the first report to demonstrate that calcium antagonists have a direct effect on a fibroblast cell line leading to a decrease of RNA synthesis. Such findings suggest that calcium-antagonist vascular effects extend beyond vascular smooth muscle cells to connective tissues associated with extracellular- matrix protein production.