title: Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation.
abstract: BACKGROUND
  Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs, an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO.
  
  
  RESULTS
  Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin, which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 mol/L), or an intravascular nitrite infusion (3 mg/h bolus, 5 mg · kg⁻¹ · h⁻¹ infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed in lambs while breathing the nitrite aerosol (≈ 20 ppb NO) but not during intravascular infusion of nitrite.
  
  
  CONCLUSIONS
  We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA. ablood@llu.edu
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
authors.forename: Hobe J
authors.initials: HJ
authors.lastname: Schroeder
authors.forename: Michael H
authors.initials: MH
authors.lastname: Terry
authors.forename: Jeanette
authors.initials: J
authors.lastname: Merrill-Henry
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Bragg
authors.forename: Kurt
authors.initials: K
authors.lastname: Vrancken
authors.forename: Taiming
authors.initials: T
authors.lastname: Liu
authors.forename: Jason L
authors.initials: JL
authors.lastname: Herring
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Sowers
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000008:administration & dosage* / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D014665:Vasodilator Agents; D009569:Nitric Oxide