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.
Weiss
Harvey R
HR
Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics and Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Doshi
Deepa
D
Sinha
Arabinda K
AK
Liu
Xia
X
Chi
Oak Z
OZ
D000818:Animals; D001345:Autoradiography; D001784:Blood Gas Analysis; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D010052:Ovariectomy; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D004958:Estradiol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate