Inhaled Nitric Oxide Therapy Increases Blood Nitrite, Nitrate, and S-Nitrosohemoglobin Concentrations in Infants With Pulmonary Hypertension

J Pediatr. 2012 Feb;160(2):245-51. doi: 10.1016/j.jpeds.2011.07.040. Epub 2011 Sep 9.


Objective: To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension.

Study design: In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12).

Results: After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change.

Conclusion: Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Female
  • Hemoglobins / metabolism*
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / drug therapy*
  • Infant
  • Infant, Newborn
  • Male
  • Nitrates / blood*
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / pharmacology*
  • Nitrites / blood*
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*


  • Hemoglobins
  • Nitrates
  • Nitrites
  • S-nitrosohemoglobin
  • Vasodilator Agents
  • Nitric Oxide