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. This difference could be due to a vasoactive effect that would improve blood flow in focal ischemia but would not be operative in global ischemia. 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. Each ring was suspended in an organ bath and isometric tension was recorded. After half-maximal contractions with either KCl or 5-hydroxytryptamine, 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 microM had no effect on both canine and guinea pig basilar arteries with or without endothelium whereas concentrations 10-160 microM further contracted the arteries in an endothelium dependent fashion, with the exception of the KCl precontracted 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.