Localized increase in nitric oxide production and the expression of nitricoxide synthase isoforms in rat uterus with experimental intrauterine infection

OBJECTIVE: We recently reported that nitric oxide was associated with incre ased mortality among pregnant rats with intrauterine infection. In our curr ent study we investigated the expression of different isoforms of nitric ox ide synthases and nitric oxide in the nonpregnant rat uterus with experimen tal intrauterine infection. STUDY DESIGN: Pathogenic Escherichia coli was inoculated into the uterine l umen of ovariectomized rats. Animals were killed after inoculation, and ute rine horns were collected for assessing nitric oxide production with high-p erformance liquid chromatography and nitric oxide synthase (type II and typ e III) protein expression with Western immunoblotting and immunofluorescenc e methods. RESULTS: (1) Nitric oxide production increased in the infected uterine horn in a time-dependent manner after intrauterine infection but did not increa se in the uninfected horn. (2) Nitric oxide synthase type ill protein conte nts did not show a difference between infected and uninfected horns, and ty pe III nitric oxide synthase was expressed by the epithelial cells and smoo th muscle cells. (3) Type II nitric oxide synthase was abundantly expressed in infected horns but was not expressed in uninfected horns. Immunofluores cence data indicated that macrophages and natural killer cells, located in the endometrial layer clustering around epithelial cells, expressed type II protein. CONCLUSION: We suggest that localized increase in type II nitric oxide synt hase expression and nitric oxide production occurs in response to intrauter ine infection and that the nitric oxide system may play a role in host resp onse to restrict the infection.