Chronic estrogen treatment increases levels of endothelial nitric oxide synthase protein in rat cerebral microvessels.
OBJECTIVE
A number of studies indicate that the female gonadal hormone, estrogen, confers protection against cerebrovascular disorders such as stroke. One postulated mechanism for these effects of estrogen is an action on the enzyme endothelial nitric oxide synthase (eNOS), which produces the vasodilatory molecule NO. We have investigated the hypothesis that estrogen increases expression of eNOS in cerebral microvessels of male and female rats.


METHODS
We measured levels of eNOS protein by Western blot in cerebral microvessels isolated from 7 groups of animals: females, ovariectomized females, ovariectomized females treated with estrogen, males, castrated males, castrated males treated with estrogen, and castrated males treated with testosterone.


RESULTS
Ovariectomized female rats treated with estrogen had 17. 4-fold greater levels of eNOS protein in cerebral microvessels than ovariectomized females, and intact females had 16.6-fold greater levels than ovariectomized females (P<0.01). In intact females, cerebral microvessel eNOS protein levels were 9.2-fold higher than those of intact males (P<0.05). Levels of eNOS protein in castrated males, castrated males treated with testosterone, and males were not different from each other. Estrogen treatment of castrated animals resulted in an 18.8-fold increase in cerebral microvessel eNOS protein (P<0.05).


CONCLUSIONS
Chronic estrogen treatment increases levels of eNOS protein in cerebral microvessels of male and female rats. This increase in eNOS protein correlates with our previous functional findings indicating that estrogen exposure increases NO modulation of cerebrovascular reactivity in both male and female animals. Upregulation of eNOS expression may contribute to the neuroprotective effect of estrogen.
McNeill
A M
AM
Department of Pharmacology, College of Medicine, University of California at Irvine, USA.
Kim
N
N
Duckles
S P
SP
Krause
D N
DN
Kontos
H A
HA
D000818:Animals; D001921:Brain / Q000098:blood supply*; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D004967:Estrogens; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat