CALCIUM-ENTRY BLOCKERS STIMULATE VASOPROLIFERATION ON THE CHICK CHORIOLLANTOIC MEMBRANE

The effect of three calcium entry blockers, nifedipine, nimodipine, an d verapamil on the vascular density of the chick chorioallantoic membr ane (CAM) was studied. Each compound was released onto the CAM for thr ee days (Days 7-10 or Days 11-14 of incubation) from Elvax polymer sus tained release pellets. Quantitation of the Vascular density was obtai ned by counting the number of intercepts between the CAM Vessels and a series of concentric circles placed over the CAM; the results are exp ressed as a vascular density index (VDI). Nifedipine released during D ays 11-14 elicited an inverted U-shaped dose-response curve in the VDI with a peak increase of 30.6% over the control. Nimodipine induced a similar, but less intense (16.9%) increase in the VDI. Peak responses for both compounds occurred with pellets containing 0.15 mu g of the d rug. Verapamil stimulated a VDI increase equivalent to nimodipine, but the response was not dose-related. Neither nifedipine nor nimodipine caused a significant increase of the VDI during Days 7-10. Verapamil w as not tested at this time. The calcium channel agonist, BAY K-8644, d id not alter the VDI; however, the vasoproliferative response to nifed ipine (0.15 mu g/pellet) was reduced 70% when an equal mass of BAY K-8 644 was incorporated also into the pellet. These experiments demonstra te a vasoproliferative effect for the three calcium entry blockers, an d support an hypothesis that their efficacy in the treatment of cardio /cerebro-vascular disease resides, in part, in their capacity to stimu late new blood vessel growth.