Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation
Open accessAbstract
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⁻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.
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Nitrite administered via inhalation or infusion is a selective pulmonary vasodilator with increased activity in hypoxia.
“Similarly, nitrite administered via inhalation or infusion is a selective pulmonary vasodilator with increased activity in hypoxia[142–144]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [142]
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Heme-NO dilates arteries via mobilization of NO moieties from a vascular intracellular NO storePreprint
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- Authors
- Blood, A. B., Schroeder, H. J., Terry, M. H., Merrill-Henry, J., Bragg, S. L., Vrancken, K., Liu, T., Herring, J. L., Sowers, L. C., Wilson, S. M., & Power, G. G.
- Affiliations
- Loma Linda University Medical Center (US)
- From the Department of Pediatrics, Division of Neonatology (A.B.B., S.L.B., K.V., T.L.), Center for Perinatal Biology (A.B.B., H.J.S., S.M.W., G.G.P.), Department of Respiratory Care (M.H.T., J.M.-H.), and Department of Biochemistry (J.L.H., L.C.S.), Loma Linda University School of Medicine, Loma Linda, CA.
- ORCID
- Venue
- Circulation
- Published
- 2011-02-15
- Volume
- 123
- Issue
- 6
- Pages
- 605-612
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3077283
- OpenAlex
- W1969103666
- Cited by
- 36
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 7
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL095973, R01HL095973)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide, pulmonary vasodilation, pulmonary hypertension, methemoglobin, free hemoglobin, hemolysis, newborn lambs, exhaled nitric oxide, pulmonary vascular resistance, nitric oxide scavenging
- MeSH terms
- Administration, Inhalation, Animals, Animals, Newborn, Hemoglobins, Hemolysis, Hypertension, Pulmonary, Lung, Nitric Oxide, Nitrites, Pulmonary Circulation, Sheep, Vasoconstriction, Vasodilator Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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