title: Increased nitrite reductase activity of fetal versus adult ovine hemoglobin.
abstract: Growing evidence indicates that nitrite, NO2-, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50-80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus.
authors.affiliation: Department of Pediatrics, Division of Neonatology, School of Medicine, Loma Linda University, Loma Linda, CA, USA. ablood@llu.edu
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
authors.forename: Mauro
authors.initials: M
authors.lastname: Tiso
authors.forename: Shilpa T
authors.initials: ST
authors.lastname: Verma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lo
authors.forename: Mahesh S
authors.initials: MS
authors.lastname: Joshi
authors.forename: Ivan
authors.initials: I
authors.lastname: Azarov
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002908:Chronic Disease; D004195:Disease Models, Animal; D004227:Dithionite / Q000737:chemistry; D005260:Female; D005312:Fetal Blood / Q000201:enzymology*; D005311:Fetal Hypoxia / Q000201:enzymology; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000201:enzymology; D007700:Kinetics; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood*; D009572:Nitrite Reductases / Q000097:blood*; D009573:Nitrites / Q000097:blood*; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D011487:Protein Conformation; D012756:Sheep
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D004227:Dithionite; D009569:Nitric Oxide; D008706:Methemoglobin; D009572:Nitrite Reductases; D010100:Oxygen