Differential effects of Ca2+ channel blockers on Ca2+ transients and cell cycle progression in vascular smooth muscle cells.

We examined the differential effects of Ca2+ channel blockers on the elevation of the cytosolic Ca2+ concentration ([Ca2+]i) and G0/G1 transition induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells in primary culture. The phase of the cell cycle was determined by an immunocytochemical analysis of cell cycle-specific nuclear antigens. [Ca2+]i was monitored by fura-2 microfluorometry. The efficacy of Ca2+ channel blockers for the inhibition of [Ca2+]i elevation induced by PDGF (NiCl2 > isradipine > verapamil = diltiazem) did not parallel that for the inhibition of cell cycle progression induced by PDGF (verapamil = diltiazem > NiCl2 > isradipine). In addition, no significant correlation was observed between the extent of [Ca2+]i elevation and the extent of G0/G1 transition. We thus conclude that the inhibitory effects of Ca2+ channel blockers on the G0)/G1 transition induced by PDGF are not simply due to their inhibitory action on the [Ca2+]i elevations but instead are due to more complex unknown factors.