17-BETA-ESTRADIOL ATTENUATES ENDOTOXIN-INDUCED EXCESSIVE NITRIC-OXIDEPRODUCTION IN OVARIECTOMIZED RATS IN-VIVO

Experiments were designed to examine the effect of 17 beta-estradiol o n 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-inject ed 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 r ats resulted in a four- to fivefold increase in circulating plasma nit rite level, significantly higher in the ovariectomized animals compare d with the sham-operated animals. The LPS-induced plasma nitrite incre ase could be prevented by dexamethasone (3 mg/kg ip) injected 1 h befo re LPS treatment. 17 beta-Estradiol (3 mu g/rat sc), administered 48 h before LPS treatment, significantly attenuated the LPS-induced elevat ion in plasma nitrite levels. This effect was comparable to that achie ved by aminoguanidine (200 mu M/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 a ssociated with excessive nitric oxide generation.