Induction of myocardial nitric oxide synthase by Coxsackie B3 virus in mice

Background inducible nitric oxide synthase (iNOS) expression is regulated b y cytokines, This study investigated whether Coxsackie group B virus (CVB) myocarditis resulted in an environment suitable for induction of NOS in the murine heart. Materials and methods Myocardium was removed from mice infected with CVB3 a nd from controls. Histology, reverse transcriptase polymerase reaction (RT- PCR) fur murine iNOS, NOS enzyme activity and immunohistochemistry were ass essed. Results Histology revealed severe myocarditis 7 days after infection with C VB3 but not in controls. RT-PCR using primers for murine iNOS detected iNOS mRNA in infected mice bur not in controls. Calcium-independent NOS activit y increased by day 5 after infection with a peak at day 7. Calcium-dependen t NOS activity was present throughout, with a trend to lower levels during peak calcium-independent activity. Immunohistochemistry revealed iNOS to be localized to inflammatory cells rather than to myocytes. Conclusion This study demonstrates the development of calcium-independent N OS activity and de novo gene transcription for iNOS in the murine myocardiu m in response to CVB3 infection. The nitric oxide produced at such high out put may act at rimes as part of the immune defence as an antiviral agent an d may be toxic to host tissue.