Comparison of the Calcium Antagonistic Activity of Nifedipine and FR34235 in the Canine Saphenous Vein

Abstract

The effects of FR34235 (FR) on contractions and 45Ca2+ uptake stimulated by depolarization (80 mM KCl) and activation of postsynaptic α1-adrenoceptors in the canine saphenous vein (CSV) were studied and compared with those of nifedipine. The 45Ca2+ uptake and contractions evoked by KCl were inhibited in a dose-dependent fashion by FR [concentration producing 50% inhibition [(IC50 = 2.0 ± 0.5 and 1.2 ± 0.3 × 10−8M, respectively)] and nifedipine (IC50 = 6.0 ± 1.0 and 4.0 ± 0.9 × 10−8M, respectively). FR was a potent inhibitor of the 45Ca2+ uptake and contractions of CSV induced by the selective α1-agonist, SK&F l-89748 (l-[1,2,3,4-tetrahydro - 8 - methoxy - 5 - (methylthio) - 2 - naphthalenamine]) (IC50 = 7.2 ± 0.7 and 7.0 ± 1.8 × 10−8M, respectively). In contrast, the contractions and 45Ca2+ uptake elicited by SK&F l-89748 were much less sensitive to nifedipine (IC50 = 6.0 ± 1.4 and 6.6 ± 0.4 × 10−8M, respectively). The results suggest the following: (a) both FR and nifedipine are potent antagonists of the voltage-dependent Ca2+ channels in CSV; and (b) FR is a more effective antagonist of receptor-operated Ca2+ entry in the saphenous vein than nifedipine.