Different Effects of Verapamil on Cytosolic Ca²⁺ and Contraction in Norepinephrine-Stimulated Vascular Smooth Muscle

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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 in-crease 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⁺.