Biopterin in the acute phase of hypoxia–ischemia in a neonatal pig model

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 °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 12 h after the insult. The concentrations of nitrite and nitrate were elevated in the cerebral cortex 12 h 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 4 h after the insult (604.8 ± 200.9 nM) and only slightly decreased after 12 h (445.9 ± 57.8 nM). In the hypothermia group, no iNOS expression was observed 12 h 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 4 h 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.