Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

Previous studies have demonstrated that nitric oxide (NO) is involved in th e uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show a bundant expression of inducible NOS with significant elevation in NO produc tion in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and in ducible NOS expression in the nonpregnant rat. In our present study, we exa mined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauter ine pathogenic Escherichia coli infection. Unlike the nonpregnant state, th e NO production in the infected uterine horn of pregnant rats was not signi ficantly elevated after bacterial inoculation compared with the contralater al uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the ut erus on infection. Moreover, intrauterine infection induced an elevated exp ression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential s timulation of NOS expression, especially the inducible isoform, and generat ion of uterine NO are lacking during pregnancy despite an elevated tumor ne crosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system . Present studies, together with our previous report that intrauterine infe ction-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complic ations associated with intrauterine infection and that the constitutively e levated uterine NO during pregnancy may help contain or even reduce the ris k of infection-related complications.