17 beta-Estradiol attenuates endotoxin-induced excessive nitric oxide production in ovariectomized rats in vivo.
Experiments were designed to examine the effect of 17 beta-estradiol on lipopolysaccharide (LPS)-induced excessive nitric oxide production in vivo. Ovariectomized and sham-operated female rats were injected with LPS (5 mg/kg ip), and different groups of ovariectomized, LPS-injected animals were treated with either 17 beta-estradiol, dexamethasone, or aminoguanidine. Nitric oxide generation was estimated by measuring plasma nitrite levels 12 h after LPS injection. LPS treatment of the rats resulted in a four- to fivefold increase in circulating plasma nitrite level, significantly higher in the ovariectomized animals compared with the sham-operated animals. The LPS-induced plasma nitrite increase could be prevented by dexamethasone (3 mg/kg ip) injected 1 h before LPS treatment. 17 beta-Estradiol (3 micrograms/rat sc), administered 48 h before LPS treatment, significantly attenuated the LPS-induced elevation in plasma nitrite levels. This effect was comparable to that achieved by aminoguanidine (200 microM/kg), an inhibitor of inducible nitric oxide synthase, injected 1 h after LPS treatment. The present findings suggest that estrogens may be beneficial in pathological conditions associated with excessive nitric oxide generation.
Kauser
K
K
Cardiovascular Department, Berlex Biosciences, Richmond, California 94806-0099, USA.
Sonnenberg
D
D
Tse
J
J
Rubanyi
G M
GM
D000704:Analysis of Variance; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006146:Guanidines; D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D004958:Estradiol; D003907:Dexamethasone; C004479:pimagedine