Effect of MK-801 on focal brain infarction in normotensive and hypertensive rats.

The effects of the noncompetitive N-methyl-D-aspartate antagonist MK-801 on infarct size and systemic variables after middle cerebral artery occlusion in spontaneously hypertensive and Fischer-344 rats were investigated. Two doses (0.5 and 5 mg/kg) administered before the induction of ischemia were studied. MK-801 significantly reduced the neocortical volume of infarction (by about 32% at both doses) in Fischer-344 rats and had no neuroprotective effects in the striatum. In contrast, MK-801 had no significant influence on either cortical or striatal infarcted volume in spontaneously hypertensive rats. The reduction or lack of MK-801-induced neuroprotection in spontaneously hypertensive rats, as compared with Fischer-344 rats, could be attributed to a reduced collateral supply in the marginal area due to difference in the morphology of the pial anastomoses and/or in the effects of ischemia and treatment on arterial pressure. The results may have major clinical implications since a great proportion of human strokes are associated with hypertension.