Inhibitory Effects of Verapamil and Nitroglycerin on Contraction and Cytosolic Ca²⁺ Levels in Cerebrovascular Smooth Muscle During Chronic Cerebral Vasospasm

Abstract

The mechanisms of the inhibitory effects of verapamil and nitroglycerin on vasospasm were investigated by measuring cytosolic Ca²⁺ level ([Ca²⁺]_i) and muscle tension in 28 normal specimens and 28 spastic vascular specimens of smooth muscle. Experimental vasospasm was produced by the two-hemorrhage method in the canine basilar artery. [Ca²⁺]_i and tension were recorded simultaneously with a fluorimeter using fura-2. High K⁺ concentration (72.4 mM) and U-46619 (thromboxane A₂ analogue, 10^-8 M) were used as stimulants, and the inhibitory effects of verapamil or nitroglycerin on muscle contraction and increased [Ca²⁺]_i were examined. Verapamil inhibited [Ca²⁺]_i and contraction in high K⁺ concentration-stimulated arteries. Verapamil inhibited [Ca²⁺]_i more strongly than contraction in U-46619-stimulated arteries. There were no significant differences in the effects of verapamil in the control and vasospasm groups. Nitroglycerin inhibited contraction with little effect on [Ca²⁺]_i in high K⁺ concentration-stimulated arteries in both the control and vasospasm groups. Nitroglycerin inhibited contraction with little effect on [Ca²⁺]_i in U-46619-stimulated arteries and the inhibitory effect was weaker in the vasospasm group than in the control group. The inhibitory effects of verapamil on muscle tension and [Ca²⁺]_i in vasospastic vessels were as strong as those in normal vessels. In contrast, the inhibitory effects of nitroglycerin were reduced in vasospastic vessels. Increased Ca²⁺ sensitivity in vasospastic vessels may have reduced the inhibitory effects of nitroglycerin.