Different effects of verapamil on cytosolic Ca2+ and contraction in norepinephrine-stimulated vascular smooth muscle.

Effects of verapamil on cytosolic Ca2+ levels ([Ca2+]cyt) and contraction in fura-2-loaded rat aorta were examined. Norepinephrine (NE) induced a greater contraction than KCl for a given increase in [Ca2+]cyt. Cumulative addition of verapamil decreased the NE-stimulated [Ca2+]cyt more strongly than contraction whereas verapamil decreased high K(+)-stimulated [Ca2+]cyt and contraction in parallel. In the presence of verapamil at a concentration needed to completely inhibit the high K(+)-induced increments, NE induced a transient increase, followed by a small sustained increase in [Ca2+]cyt which averaged 25% of that in the absence of verapamil. These changes were followed by a sustained contraction which averaged 60% of that in the absence of verapamil. In Ca2(+)-free solution, NE induced only a transient increase in [Ca2+]cyt whereas it induced a transient contraction, followed by a small sustained contraction. The second application of NE induced a small sustained contraction (10% of that in the presence of Ca2+) without increasing [Ca2+]cyt. These changes were not affected by verapamil. These results suggest that verapamil inhibits NE-induced increase in [Ca2+]cyt, but not the Ca2(+)-sensitization or Ca2(+)-independent contraction, and this may be the reason why the NE-induced contraction is less sensitive to verapamil than that induced by high K+.