Developmental changes in NO bioavailability in fetal erythrocytes

S-nitrosohemoglobin (HbSNO), where hemoglobin (Hb) is nitrosated at Cysbeta93, presumably controls delivery of the vasorelaxant nitric oxide (NO) to hypoxic tissues in an oxygen-sensitive manner. Little is known about how Hb regulates NO bioavailability during fetal development. A study was planned to determine the levels of HbSNO and HbFe(II)NO (NO bound to FeII of heme) in the cord blood of newborn infants of different gestational ages and establish their relationship with the levels of fetal Hb (HbF). Blood samples were collected from umbilical cord obtained from normal newborns between 24 and 41 weeks of gestation. Determinations of HbSNO and HbFe(II)NO were performed using chemiluminescence. The proportion of HbF was determined by HPLC. There were 11 preterm (24-34 weeks of gestation) and 11 term infants (37-41 weeks of gestation). The levels of HbSNO varied from 0.37 to 1.72 x 10(-5) mol/mol heme. There was a significant correlation with gestational age (r2 = 0.46, P = 0.0005) due to the effect of the decrease in the amount of HbF (r2 = 0.81, P < 0.0001). The relationship of HbFe(II)NO was not affected by gestational age or the level of HbF (mean 1.68+/-1.15 x 10(-5) mol/mol heme). Under physiological in utero conditions, fetal erythrocytes have lower levels of HbSNO, which increase in the later stage of fetal development. The levels of HbSNO in the fetal red cell are dependent on the level of adult Hb (HbA). The low HbSNO levels at physiological fetal O2 saturations during early development could protect the fetal circulation from an excess release of NO and O2.