Calcium entry blockers stimulate vasoproliferation on the chick chorioallantoic membrane

The effect of three calcium entry blockers, nifedipine, nimodipine, and verapamil on the vascular density of the chick chorioallantoic membrane (CAM) was studied. Each compound was released onto the CAM for three days (Days 7-10 or Days 11-14 of incubation) from Elvax polymer sustained release pellets. Quantitation of the vascular density was obtained by counting the number of intercepts between the CAM vessels and a series of concentric circles placed over the CAM; the results are expressed as a vascular density index (VDI). Nifedipine released during Days 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 microgram of the drug. 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 was not tested at this time. The calcium channel agonist, BAY K-8644, did not alter the VDI; however, the vasoproliferative response to nifedipine (0.15 microgram/pellet) was reduced 70% when an equal mass of BAY K-8644 was incorporated also into the pellet. These experiments demonstrate a vasoproliferative effect for the three calcium entry blockers, and support an hypothesis that their efficacy in the treatment of cardio/cerebro-vascular disease resides, in part, in their capacity to stimulate new blood vessel growth.