Induction of myocardial nitric oxide synthase by Coxsackie B3 virus in mice.
BACKGROUND
Inducible nitric oxide synthase (iNOS) expression is regulated by cytokines. This study investigated whether Coxsackie group B virus (CVB) myocarditis resulted in an environment suitable for induction of NOS in the murine heart.


METHODS
Myocardium was removed from mice infected with CVB3 and from controls. Histology, reverse transcriptase polymerase reaction (RT-PCR) for murine iNOS, NOS enzyme activity and immunohistochemistry were assessed.


RESULTS
Histology revealed severe myocarditis 7 days after infection with CVB3 but not in controls. RT-PCR using primers for murine iNOS detected iNOS mRNA in infected mice but not in controls. Calcium-independent NOS activity increased by day 5 after infection with a peak at day 7. Calcium-dependent 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.


CONCLUSIONS
This study demonstrates the development of calcium-independent NOS activity and de novo gene transcription for iNOS in the murine myocardium in response to CVB3 infection. The nitric oxide produced at such high output may act at times as part of the immune defence as an antiviral agent and may be toxic to host tissue.
Robinson
N M
NM
King's College Hospital Medical School, London, UK. nick1robinson@compuserve.com
Zhang
H Y
HY
Bevan
A L
AL
De Belder
A J
AJ
Moncada
S
S
Martin
J F
JF
Archard
L C
LC
D000818:Animals; D001483:Base Sequence; D003384:Coxsackievirus Infections / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D006321:Heart / Q000821:virology*; D007150:Immunohistochemistry; D007700:Kinetics; D051379:Mice; D009205:Myocarditis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014774:Virulence
D017931:DNA Primers; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse