[Effect of diltiazem on experimental cerebral vasospasm incomparison with effects of cinnarizine, verapamil and nifedipine].
The contractile activity of arterial muscle cells is controlled by the intercellular free Ca2+ concentration. The membrane systems of both the cell surface and internal organs, seem to be responsible for controlling the myoplasmic Ca2+ level. The mechanism of action of Ca2+ antagonists, typified by verapamil and nifedipine, has been postulated to be a blockade of transmembrane calcium influx. In this study, the vasodilating effect of diltiazem on experimental cerebral vasospasm in vivo was examined using dogs and was compared with those of cinnarizine, verapamil and nifedipine which have already been reported by us. Cerebral vasospasms were induced in adult dogs by injecting 5 ml of fresh arterial blood into the cisterna magna. 10(-6)M diltiazem was injected by one shot into the vertebral artery with cerebral vasospasm. Dilatation of the cerebral arteries were monitored by angiography after administration of diltiazem. Blood pressure, intracranial pressure and pulse rate were measured during intravenous application of the drug in normal animals. Administration of diltiazem released the vasospasm for 30 minutes comparable to the times of the other Ca2+ antagonists. Diltiazem had cerebral vasodilator actions similar to cinnarizine at doses that did not decrease systemic blood pressure, while the other drugs decreased intracranial pressure slightly and nifedipine decreased pulse rate slightly. Therefore, we consider diltiazem to be satisfactory for the treatment of experimental cerebral vasospasm.
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002936:Cinnarizine / Q000627:therapeutic use; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007427:Intracranial Pressure / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D009543:Nifedipine / Q000627:therapeutic use; D011674:Pulse / Q000187:drug effects; D014700:Verapamil / Q000627:therapeutic use
D001552:Benzazepines; D002936:Cinnarizine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine