Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood.
The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels.
Tsuji
T
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Department of Pharmacology, University of Albeta, Edmonton, Canada.
Cook
D A
DA
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D001790:Blood Physiological Phenomena; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D012701:Serotonin; D009553:Nimodipine; D011189:Potassium Chloride; D013917:Thrombin