Effect of nitric oxide on the transport and release of oxygen in fetal blood.
It is well known that nitric oxide (NO), the most important vasodilator agent, plays an important role in lowering vascular resistance in the human umbilical-placental circulation and that its deficiency is related to the pathogenesis of pre-eclamptic disorder. Besides it has recently been demonstrated that human hemoglobin (HbA) is able to transport nitric oxide, as S-nitrosohemoglobin (SNO-Hb), from the arterial to the venous blood. In the present study we examine the functional properties of the adult and fetal nitrosated hemoglobins to see if the double transport of oxygen and NO may influence the fetal oxygenation and the relation between maternal and fetal blood. Our results show that S-nitrosation significantly increases the oxygen affinity of the adult Hb (HbA) with respect to native protein (no-nitrosated) while the functional properties of HbF are less influenced. The oxygen affinity modification, found for SNO-HbA, was ascribed to the nitrosation of cysteine beta 93: really, the same residue is also present in the gamma chains of fetal hemoglobin, while the increase of affinity is less evidenced; hence, it is probable that the 39 aminoacidic substitutions between beta and gamma chains allay the effects of S-nitrosation. As regards the physiological modulators (protons, chloride ions, 2,3-diphosphoglyceric acid, and temperature), they influence the oxygen affinity of the two hemoglobins S-nitrosated, in equal mode with respect to the native forms determining the same variation on the oxygen affinity. Hence, our results evidence the fact that the NO release by SNO-HbA "in vivo" would be limited to regions of extremely low oxygen tension (such as hypoxic regions), while in fetus, SNO-HbF would unload nitric oxide and oxygen at pressure values close to normal.
Clementi
Maria Elisabetta
ME
CNR Institute Chimica del riconoscimento Molecolare, Catholic University, Largo F. Vito 1, 00168 Rome, Italy. e.clementi@uniserv.ccr.rm.cnr.it
Orsini
Federica
F
Schininà
Maria Eugenia
ME
Noia
Giuseppe
G
Giardina
Bruno
B
D001769:Blood / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006441:Hemoglobin A / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009569:Nitric Oxide / Q000494:pharmacology*; D009584:Nitrogen / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011312:Pressure; D013696:Temperature; D014470:Umbilical Cord / Q000378:metabolism
D006454:Hemoglobins; C103574:S-nitrosohemoglobin; D009569:Nitric Oxide; D006441:Hemoglobin A; D005319:Fetal Hemoglobin; D009584:Nitrogen; D010100:Oxygen