IN-VITRO CEREBRAL VASOACTIVE EFFECTS OF MK-801

MK-801, although more consistently neuroprotective in focal ischemia, has had more variable success in the management of global ischemia. Th is difference could be due to a vasoactive effect that would improve b lood flow in focal ischemia but would not be operative in global ische mia. Therefore, a possible direct cerebrovascular effect of MK-801 was investigated in vitro in basilar arteries from 13 dogs and 16 guinea pigs. Two rings were obtained from each animal; in one the endothelium was removed and in the other the endothelium was maintained intact. E ach ring was suspended in an organ bath and isometric tension was reco rded. After half-maximal contractions with either KCl or 5-hydroxytryp tamine, a dose of MK-801 or the same volume of saline was added to the bath. MK-801 concentrations between 0.1 and 1.0 mu M had no effect on both canine and guinea pig basilar arteries with or without endotheli um whereas concentrations 10-160 mu M further contracted the arteries in an endothelium dependent fashion, with the exception of the KC1 pre contracted endothelium intact canine artery. Higher concentrations of MK-801 tended to dilate the arteries and the dilation was endothelium independent. Thus, MK-801 has dose-dependent cerebral vascular effects and our results may explain some of the conflicting results of MK-801 on CBF.