Effects of felodipine, nifedipine and verapamil on cytosolic Ca 2+ and contraction in vascular smooth muscle

Abstract

The inhibitory effects of felodipine, nifedipine and verapamil were compared in vascular smooth muscle. In rat aorta, these inhibitors attenuated the high K +-induced contraction with a parallel decrease in the cytosolic Ca 2+ level ([Ca 2+] i). Maximal inhibition was obtained with 10 nM felodipine, 100 nM nifedipine and 10 μM verapamil. The inhibitory effects were antagonized by an increase in external Ca 2+ concentration to 6.5 mM and the addition of a Ca 2+ channel activator, 100 nM Bay k 8644. These inhibitors also attenuated the contraction induced by norepinephrine although these effects were weaker than those on high K +-induced contraction. Furthermore, these inhibitors attenuated the norepinephrine-stimulated [Ca 2+] i more strongly than contraction. In contrast, none of these inhibitors inhibited the transient increase in [Ca 2+] i and muscle tension induced by norepinephrine in Ca 2+-free solution and the Ca 2+-induced contraction in permeabilized smooth muscle. These results suggest that felodipine, nifedipine and verapamil inhibit smooth muscle contraction by inhibiting Ca 2+ channels at concentrations which do not change Ca 2+ release or Ca 2+ sensitivity of contractile elements.