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 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.
Fujioka
Hiroki
H
Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi Abeno-ku, Osaka 545-8585, Japan. hfujioka@msic.med.osaka-cu.ac.jp
Shintaku
Haruo
H
Nakanishi
Hidehiko
H
Kim
Tae-Jang
TJ
Kusuda
Satoshi
S
Yamano
Tsunekazu
T
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001708:Biopterins / Q000032:analysis / Q000097:blood*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D020520:Brain Infarction / Q000097:blood / Q000503:physiopathology; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010100:Oxygen / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology; D034421:Sus scrofa; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D001708:Biopterins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen