Possible involvement of nitric oxide in estrogen-induced uterine edema in the immature rat

We examined whether nitric oxide mediates estrogen-induced uterine edema in the immature rat. Immature Wistar rats (19-21 days) received estradiol-17 beta (E2) in a single sc dose of 10 micrograms/animal and 6 h later the animals were sacrificed and the changes in uterine wet and dry weights were determined. E2 treatment caused a 93% increase in uterine wet weight (control, N = 6, 39.88 +/- 3.2 mg; E2 treated, N = 6, 76.8 +/- 4.9 mg), but not in dry weight, suggesting that it induces uterine edema. Pretreatment with L-nitroarginine methyl ester (L-NAME), a competitive antagonist of nitric oxide synthetase, at doses of 10 and 20 mg/kg, ip, caused a dose-related reduction (59 and 86%) in the uterine wet weight increase induced by E2. Furthermore, L-arginine (300-600 mg/kg, sc), the nitric oxide precursor, was able to reverse L-NAME (20 mg/kg)-induced decreases in uterine weight by 47 and 62%, respectively. The results suggest that nitric oxide is the principal mediator involved in estrogen-induced uterine edema in the immature rat.