To clarify the participation of inducible NOS (iNOS) in the
hypoxia-
ischemia, we examined iNOS and its
tetrahydrobiopterin co-factor in the cerebral cortex and plasma in a newborn-piglet model. We also investigated the role of
hypothermia in iNOS expression and
biopterin production. Male newborn piglets were ventilated 6%
oxygen for 45 min. Their common carotid arteries were clamped during
hypoxia. Then they were resuscitated with 30%
oxygen (HI group). Piglets of the
hypothermia group were treated as the HI group and their body was cooled to 35.5 degrees C after hypoxic-ischemic insults.
Sham-treated piglets were also reserved. In the HI group, iNOS was present in neurons and macrophages of the cerebral cortex 12h after the insult. The concentrations of
nitrite and
nitrate were elevated in the cerebral cortex 12h after hypoxic-ischemic insults but the
biopterin level was unchanged. The plasma
biopterin concentration after the insult (377.9+/-78.7 nM) was five times higher than before the insult (80.1+/-4.3 nM); this level peaked 4h after the insult (604.8+/-200.9 nM) and only slightly decreased after 12h (445.9+/-57.8 nM). In the
hypothermia group, no iNOS expression was observed 12h after the insult. The plasma
biopterin concentration after the insult (464.2+/-92.3 nM) was similar to that in the HI group, but was suppressed by 4h of
hypothermia (229.3+/-106.8 nM). In this study, neuronal iNOS expression and increase of NO production were found in the acute phase of
hypoxia-
ischemia. Brain
biopterin did not increase in
hypoxia-
ischemia although plasma
biopterin was five-fold elevated. The discrepancy may also affect hypoxic-ischemic organ damage.