17Beta-estradiol blocks NMDA-induced increases in regional cerebral O(2) consumption.

We tested the hypothesis that 17beta-estradiol would reduce the cerebral O(2) consumption response to stimulation of N-methyl-D-aspartate (NMDA) receptors. We determined NMDA receptor density in 10 ovariectomized Wistar female rats equally divided into a control group and 17beta-estradiol (500 microg/21 days) treated group. An autoradiographic assay using 125I-MK-801, an NMDA antagonist, was used to measure specific binding to NMDA receptors. Another 14 ovariectomized rats were separated into 17beta-estradiol and control groups to determine cerebral blood flow (14C-iodoantipyrine) and O(2) consumption (microspectrophotometry). 17Beta-estradiol caused a 20% decrease in specific binding to cortical NMDA receptors. After topical cortical stimulation with 10(-3)M and 10(-4)M NMDA, blood flow increased significantly in control from 73+/-5 in the saline treated cortex to 110+/-8 ml/min/100 g with 10(-3)M NMDA. In contrast, there was no significant change in blood flow in the 17beta-estradiol treated animals. Cerebral O(2) extraction increased significantly in the 10(-3)M NMDA treated cortex in both groups. Cerebral O(2) consumption in the control group significantly increased by 53%, from 3.7+/-0.2 to 5.7+/-0.5 with 10(-4)M NMDA and 72% to 6.4+/-2.4 ml O(2)/min/100 g with 10(-3)M NMDA. The 17beta-estradiol group demonstrated no significant difference between the saline treated and NMDA treated cortex. Thus, 17beta-estradiol blocked the effects of NMDA on cerebral O(2) consumption and this was associated with a slightly decreased number of NMDA receptors.