Nitric oxide synthase inhibition and the uterotrophic response to oestrogen in immature rats

The role of nitric oxide in the uterotrophic action of oestradiol after 6 h or 72 h was studied in immature (19-21 days old) female Wistar rats by use of L-arginine, the amino acid from which nitric oxide is synthesized, and N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. Oestradiol at single s.c. doses of 2.5, 5.0 and 10.0 micrograms per rat induced dose-dependent uterine oedema in 6 h. L-NAME (10 and 20 mg kg-1, i.p.) administered 30 min before oestradiol (10 micrograms per rat) injection suppressed the formation of uterine oedema in a dose-related manner. This action of L-NAME on oestradiol-induced uterine oedema was effectively blocked by pretreatment of rats with L-arginine (600 mg kg-1, s.c.), a precursor of nitric oxide, but not by L-lysine, an amino acid not involved in the generation of nitric oxide. In addition, L-NAME at similar doses significantly prevented oestradiol-induced (3 micrograms per rat, s.c. on three successive days) increases in uterine growth after 72 h; however, this effect was mitigated by L-arginine (600 mg kg-1). These results suggest the involvement of an L-arginine-nitric oxide system in the oestradiol-induced uterotrophic effect in immature rats.