Comparative Experimental Studies of Few L-Type and T-Type Ca2+ Channel Blockers Against In-Ovo and In-Vitro Models of Angiogenesis

Angiogenesis is the development of new blood vessels from pre-existing one. The ion-channels on endothelium plays vital role in cell proliferation and related angiogenesis. We aimed to investigate the effects of L-type (Verapamil and Diltiazem) and T-type (Ethosuximide) Calcium Channel Blockers (CCBs) on neovascularization. The effects on neovascularization were investigated by in-ovo (CAM, Chick Chorioallantoic membrane) and in-vitro (aortic ring assay) methods. Each test drug was tested for at least 3 doses and the anti-angiogenic effect was compared with Suramin as standard and normal control groups. Various vital parameters were recorded during the experiment like the number of blood capillaries, sprouts formation, angiogenic score etc. The L-type Ca2+ channel blockers Verapamil at the dose of 50 mu M, 110 and 220 mu M/disk has shown significant (p < 0.001) reduction in the number of branching points in CAM assay. For the further confirmation, angiogenic activity was evaluated in vitro by rat aortic ring assay method; the area of sprouts was reduced by the medium and high dose of verapamil. Diltiazem has demonstrated modest anti-angiogenic activity by both the models, whereas T-type calcium channel blocker ethosuximide has not shown any effect on the neovascularization. Among all the tested drugs verapamil has shown the promising anti-angiogenic property. Thus verapamil and diltiazem may have anti-angiogenic activity defines novel beneficial effects in angiogenic mediated pathological conditions in addition to their main indications in cardiovascular complications.