Intrauterine hypoxia-ischemia alters nitric oxide synthase expression and activity in fetal and neonatal rat brains

The effects of intrauterine hypoxia-ischemia (HI) on nitric oxide synthase (NOS) activity and on expression of NOS isoforms were investigated in fetal and neonatal rat brains. Rat fetuses were subjected to either a 30-min intrauterine HI insult or a sham operation (SH) on gestational day 17 (G17). NOS activity in the homogenate of the rat brain was detectable on G17 and increased with age. NOS activity in the HI group was 20-30% higher than in the SH group from 6 to 48 h after the HI, but was 30% lower than in the SH group from postnatal day 8 to 14. Expression of the inducible NOS (iNOS) mRNA, as examined by RT-PCR, was increased as compared to the SH group from 6 to 24 h after the HI surgery. Expression of the constitutive neuronal NOS (nNOS) mRNA was reduced in the HI group from 24 h after the HI surgery up to postnatal day 14. Immunoblotting data have shown that alterations in NOS isoform protein expression caused by the intrauterine HI were consistent with the mRNA expression data. The overall results indicate that prenatal HI has long-lasting effects on function and expression of NOS in fetal and neonatal rat brains and that the altered NOS activity may be associated with prenatal HI-induced neurological abnormalities.