CALCIUM INFLUX MODULATES DNA-SYNTHESIS AND PROLIFERATION IN A7R5 VASCULAR SMOOTH-MUSCLE CELLS

In A7r5 vascular smooth muscle cultures basal Ca2+ influx was higher in growing versus quiescent cells (P < 0.05), due primarily to a five-fold increase in dihydropyridine-inhibitable Ca2+ influx (P < 0.005). Verapamil decreased [H-3]thymidine incorporation in a concentration dependent fashion with a significant 6 +/- 2% inhibition at 0.1-mu-M and a maximal inhibition of 67 +/- 2% at 100-mu-M. Similarly, nitrendipine inhibited fetal calf serum-stimulated [H-3]thymidine incorporation with a threshold concentration of 1 nM and a maximal inhibition of 79 +/- 12% at 10-mu-M. In quiescent cells, verapamil (10-mu-M) inhibited the increases in [H-3]thymidine incorporation stimulated by fetal calf serum, serotonin, vasopressin or 12-0-tetradecanoyl phorbol-13-acetate by 37-43% (P < 0.001 vs. control for all). Finally, verapamil (100-mu-M) and nitrendipine (10-mu-M) inhibited proliferation by 39 +/- 10 and 20 +/- 6%, respectively (P < 0.01 and 0.02 vs. control, respectively). Thus in A7r5 cells, proliferation is associated with increased Ca2+ influx via dihydropyridine-sensitive Ca2+ channels and organic Ca2+ channel antagonists inhibit DNA synthesis and cell proliferation.