Treatment with 17-beta-estradiol reduces superoxide production in aorta of ovariectomized rats.
OBJECTIVE
Oxidant stress contributes to vascular injury and atherosclerosis. We hypothesized that estrogen treatment of ovariectomized rats decreases O(2)(-) by decreasing the activity of NAD(P)H oxidase and this reduction in O(2)(-) could have a vasculoprotective effect.


RESULTS
Ovariectomized rats were treated with 17-beta-estradiol E2 (0.25mg) or oil placebo for 21 days. Aorta were removed for contractility studies and O(2)(-) production was measured by lucigenin enhanced chemiluminescence (230 and 5microM). E2 treatment decreased basal O(2)(-) production but did not alter NADH or NADPH stimulated O(2)(-) production. Total p47phox and p47phox in membrane fractions of cardiac tissue were decreased, which suggests less activation of NAD(P)H oxidase in E2 treated rats. E2 did not change expression of other components of NAD(P)H oxidase in heart, lung, spleen and diaphragm. Expression of eNOS was also lower in E2 treated rats. E2 did not affect the contractile response to phenylepherine, dilation with acetylcholine, dilation with superoxide dismutase or constriction with l-NAME. This argues against changes in bioavailable NO.


CONCLUSIONS
E2 decreases activation of p47phox and O(2)(-) production by NAD(P)H oxidase. This did not affect contractile properties of the vessel, but could still potentially alter cell signaling from oxidant increasing stresses.
Florian
Maria
M
McGill University Health Centre, Division of Critical Care, Royal Victoria Hospital, 687 Pine Av W, Montreal, Que., Canada H3A 1A1.
Freiman
Anatoli
A
Magder
Sheldon
S
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D000975:Antioxidants; D010750:Phosphoproteins; D013481:Superoxides; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1