Inhibitory effects of verapamil and nitroglycerin on contraction and cytosolic Ca2+ levels in cerebrovascular smooth muscle during chronic cerebral vasospasm.
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.
Tanaka
Y
Y
Department of Surgical Neurology, Jichi Medical School, Tochigi.
Masuzawa
T
T
Saito
M
M
Yamada
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects*; D002908:Chronic Disease; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D020301:Vasospasm, Intracranial / Q000188:drug therapy*; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014665:Vasodilator Agents; D014700:Verapamil; D005996:Nitroglycerin; D011188:Potassium