The contractile activity of arterial muscle cells is controlled by intracellular free Ca concentration. The membrane system, both of cell surface and internal organs, seemed to be responsible for controlling the myoplasmic Ca level. Calcium antagonists block cellular Ca in arterial strips in vitro.
In this study, the vasodilating effect of several Ca antagonists on late spasms in vivo was examined using dogs. Cinnarizine (Eisai), nifedipine (Bayer), verapamil (Eisai) and sodium nitroprusside were used as Ca antagonists.
Experimental vasospasms were induced in adult dogs by injecting about 5 ml, of fresh arterial blood into the cisterna magna.
Doses in this experiment were determined according to the drug's effectiveness in relaxing the contracted bovine basilar artery in Krebs solution. 5-HT-induced contraction was inhibited to about 20% of the maximum tension by 10
-6 M cinnarizine. The presence of 10
-6 M cinnarizine abolished K
+-induced contraction almost completely. Similar results were obtained with verapamil and sodium nitroprusside. The suitable dose of nifedipine was 10
-8 M. The required dose of each drug was injected by one shot into the vertebral artery of a dog with cerebral vasospasms. Dilatation of the cerebral arteries was monitored by angiography 5, 15 and 30 minutes after administration of the drugs. Blood pressure, intracranial pressure and pulse rate were measured during intravenous application of these drugs in normal dogs.
Administration of Ca antagonists-cinnarizine, verapamil, sodium nitroprusside and nifedipine-released the late spasm in vivo for 15 to 30 minutes. Cinnarizine had no effect on blood pressure, intracranial pressure and pulse rate, while the other drugs decreased the blood pressure. Verapamil also decreased the pulse rate slightly. Therefore, cinnarizine gave the most satisfactory results. Sodium nitroprusside seemed to be dangerous because it markedly decreased blood pressure and increased intracranial pressure.
The author concludes, in general, that administration of any Ca antagonist is quite useful for the treatment of experimental late vasospasms.
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