In vitro and in vivo kinetic handling of nitrite in blood: effects of varying hemoglobin oxygen saturation.
Growing evidence suggests that nitrite, acting via reduction to nitric oxide by deoxyhemoglobin, may play an important role in local control of blood flow during hypoxia. To investigate the effect of hypoxia (65 Torr arterial Po(2)) on the kinetic properties of nitrite, a bolus injection of sodium nitrite (10 mg/kg iv) was given to normoxic or hypoxic newborn lambs, and the time course of plasma nitrite and methemoglobin (MetHb) concentrations was measured. The in vivo kinetics of nitrite disappearance from plasma were biphasic and were not affected by hypoxia. Changes in MetHb, a product of the nitrite-hemoglobin reaction, also did not differ with the level of oxygenation. Hypoxia potentiated the hypotensive effects of nitrite on pulmonary and systemic arterial pressures. The disappearance of nitrite from plasma was equivalent to the increase in MetHb on a molar basis. In contrast, nitrite metabolism in sheep blood in vitro resulted in more than one MetHb per nitrite equivalent under mid- and high-oxygenation conditions: oxyhemoglobin (HbO(2)) saturation = 50.3 +/- 1.7% and 97.0 +/- 1.3%, respectively. Under the low-oxygenation condition (HbO(2) saturation = 5.2 +/- 0.9%), significantly less than 1 mol of MetHb was produced per nitrite equivalent, indicating that a significant portion of nitrite is metabolized through pathways that do not produce MetHb. These data support the idea that the vasodilating effects of nitrite are potentiated under hypoxic conditions due to the reduction of nitrite to nitric oxide by deoxyhemoglobin.
Blood
Arlin B
AB
Center for Perinatal Research and Division of Neonatology, Loma Linda University School of Medicine, CA 92354, USA. ablood@llu.edu
Power
Gordon G
GG
D000818:Animals; D006454:Hemoglobins / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D007267:Injections; D008706:Methemoglobin / Q000378:metabolism; D009573:Nitrites / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism*; D012756:Sheep; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation
D006454:Hemoglobins; D009573:Nitrites; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D008706:Methemoglobin; D012977:Sodium Nitrite