Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation

Arlin B. Blood, Hobe J. Schroeder, Michael H. Terry, Jeanette Merrill-Henry, Shannon L. Bragg, Kurt Vrancken, Taiming Liu, Jason L. Herring, Lawrence Sowers, Sean M. Wilson, Gordon G. Power

Research output: Contribution to journalArticle

28 Citations (Scopus)

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. Methods and 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 • h 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.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalCirculation
Volume123
Issue number6
DOIs
StatePublished - Feb 15 2011
Externally publishedYes

Fingerprint

Nitrites
Hemolysis
Vasoconstriction
Nitric Oxide
Lung
Aerosols
Hemoglobins
Pulmonary Hypertension
Gases
Sodium Nitrite
Methemoglobin
Pulmonary Circulation
Vasodilator Agents
Vasodilation
Vascular Resistance
Respiration
Blood Pressure
Pressure

Keywords

  • hemoglobin
  • hypertension, pulmonary
  • nitric oxide
  • nitrite
  • vasodilation

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Blood, A. B., Schroeder, H. J., Terry, M. H., Merrill-Henry, J., Bragg, S. L., Vrancken, K., ... Power, G. G. (2011). Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation. Circulation, 123(6), 605-612. https://doi.org/10.1161/CIRCULATIONAHA.110.001073

Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation. / Blood, Arlin B.; Schroeder, Hobe J.; Terry, Michael H.; Merrill-Henry, Jeanette; Bragg, Shannon L.; Vrancken, Kurt; Liu, Taiming; Herring, Jason L.; Sowers, Lawrence; Wilson, Sean M.; Power, Gordon G.

In: Circulation, Vol. 123, No. 6, 15.02.2011, p. 605-612.

Research output: Contribution to journalArticle

Blood, AB, Schroeder, HJ, Terry, MH, Merrill-Henry, J, Bragg, SL, Vrancken, K, Liu, T, Herring, JL, Sowers, L, Wilson, SM & Power, GG 2011, 'Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation', Circulation, vol. 123, no. 6, pp. 605-612. https://doi.org/10.1161/CIRCULATIONAHA.110.001073
Blood, Arlin B. ; Schroeder, Hobe J. ; Terry, Michael H. ; Merrill-Henry, Jeanette ; Bragg, Shannon L. ; Vrancken, Kurt ; Liu, Taiming ; Herring, Jason L. ; Sowers, Lawrence ; Wilson, Sean M. ; Power, Gordon G. / Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation. In: Circulation. 2011 ; Vol. 123, No. 6. pp. 605-612.
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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. Methods and 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 • h 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.",
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AU - Bragg, Shannon L.

AU - Vrancken, Kurt

AU - Liu, Taiming

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AU - Wilson, Sean M.

AU - Power, Gordon G.

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