Estrogen treatment enhances nitric oxide bioavailability in normotensive but not hypertensive rats.
BACKGROUND
The effects of estrogen on endothelial function remain controversial. Endothelial function is perturbed in hypertension. We aimed to determine whether pre-existing hypertension can modify endothelial-dependent responses to estrogen.


METHODS
We compared the effects of estrogen replacement on endothelial function in healthy female adult Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP). Basal and carbachol-stimulated nitric oxide (NO) bioavailability were studied in carotid artery rings in ovariectomized animals treated with estrogen or placebo for 2 weeks in vivo, or after 1 h of incubation in vitro. Basal NO bioavailability was defined as the increase in pressor responses in phenylephrine in the presence of NO synthase blockade. Superoxide (O(2)(-)) levels in aortas were measured by lucigenin chemiluminescence and endothelial NO synthase (eNOS) protein levels by Western blotting.


RESULTS
Basal NO bioavailability was increased in WKY treated with estrogen for 2 weeks compared to placebo. In contrast, no change in NO bioavailability was observed in SHRSP. The O(2)(-) levels were higher in SHRSP than in WKY but unaffected by estrogen treatment in either strain. In WKY, but not in SHRSP, estrogen caused upregulation of eNOS. Similarly in vitro exposure to estrogen increased NO bioavailability in WKY but had no effect in SHRSP. In WKY, co-exposure to estrogen and LY294002, a PI3 kinase inhibitor, abrogated the effect of estrogen.


CONCLUSIONS
The inability of estrogen to improve endothelial function in SHRSP may relate to a defect in eNOS activation pathways in this hypertensive rat strain.
Hamilton
Carlene A
CA
BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, Scotland. c.a.hamilton@clinmed.gla.ac.uk <c.a.hamilton@clinmed.gla.ac.uk>
Groves
Samantha
S
Carswell
Hilary V O
HV
Brosnan
M Julia
MJ
Graham
Delyth
D
Dominiczak
Anna F
AF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010656:Phenylephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011960:Receptors, Estrogen / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase