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

OBJECTIVE: We recently reported that nitric oxide was associated with increased mortality among pregnant rats with intrauterine infection. In our current study we investigated the expression of different isoforms of nitric oxide synthases and nitric oxide in the nonpregnant rat uterus with experimental intrauterine infection. STUDY DESIGN: Pathogenic Escherichia coli was inoculated into the uterine lumen of ovariectomized rats. Animals were killed after inoculation, and uterine horns were collected for assessing nitric oxide production with high-performance liquid chromatography and nitric oxide synthase (type II and type III) protein expression with Western immunoblotting and immunofluorescence methods. RESULTS: (1) Nitric oxide production increased in the infected uterine horn in a time-dependent manner after intrauterine infection but did not increase in the uninfected horn. (2) Nitric oxide synthase type III protein contents did not show a difference between infected and uninfected horns, and type III nitric oxide synthase was expressed by the epithelial cells and smooth muscle cells. (3) Type II nitric oxide synthase was abundantly expressed in infected horns but was not expressed in uninfected horns. Immunofluorescence 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 synthase expression and nitric oxide production occurs in response to intrauterine infection and that the nitric oxide system may play a role in host response to restrict the infection.