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Biological activity of nitric oxide in the plasmatic compartment
Open accessAbstract
There exist reaction products of nitric oxide (NO) with blood that conserve its bioactivity and transduce an endocrine vasomotor function under certain conditions. Although S-nitrosated albumin has been considered the major species subserving this activity, recent data suggest that additional NO species, such as nitrite, nitrated lipids, N-nitrosamine, and iron-nitrosyl complexes, may contribute. We therefore examined the end products of NO reactions in plasma and blood in vitro and in vivo by using reductive chemiluminescent assays and electron paramagnetic resonance spectroscopy. We found that NO complexes in plasma previously considered to be S-nitrosated albumin were <10 nM after elimination of nitrite and were mercury-stable, consistent with iron-nitrosyl or N-nitrosamine complex. During clinical NO gas inhalation protocols or in vitro NO donor treatment of human plasma, S-nitroso-albumin did not form with NO exposure <2 microM, but plasma methemoglobin was detectable by paramagnetic resonance spectroscopy. Consistent with this formation of methemoglobin, human plasma was found to consume approximately 2 microM NO at a rate equivalent to that of hemoglobin. This NO consumption was mediated by the reaction of NO with plasma haptoglobin-hemoglobin complexes and limited slower reaction pathways required for S-nitrosation. These data suggest that high-affinity, metal-based reactions in plasma with the haptoglobin-hemoglobin complex modulate plasmatic NO reaction products and limit S-nitrosation at low NO flux. The studies further suggest that alternative NO reaction end products in plasma, such as nitrite, N-nitrosamines, iron-nitrosyls, and nitrated lipids, should be evaluated in blood NO transport along the vasculature.
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“It was also shown that the addition of NO to blood generates significant concentrations of plasma nitrite that involved copper oxidation, which was found to be ceruloplasmin dependent NO oxidation [78, 79].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [79]
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Metadata
- Authors
- Wang, X., Tanus-Santos, J. E., Reiter, C. D., Dejam, A., Shiva, S., Smith, R. D., Hogg, N., & Gladwin, M. T.
- Affiliations
- National Institutes of Health (US)
- Critical Care Medicine Department, Warren G. Magnuson Clinical Center, Laboratory of Chemical Biology, and Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, and Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1662; and Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226
- Corresponding author
- Gladwin, Mark T.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-07-16
- Volume
- 101
- Issue
- 31
- Pages
- 11477-11482
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC509225
- OpenAlex
- W2081108089
- Cited by
- 164
- References
- 49
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 15
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, plasma nitric oxide, S-nitrosylation, iron nitrosyl complexes, nitrosamines, nitrite, hemoglobin-haptoglobin complex, methemoglobin, nitric oxide donors, vasomotor function
- MeSH terms
- Administration, Inhalation, Haptoglobins, Hemoglobins, Humans, Iron, Methemoglobin, Nitric Oxide, Nitrites, Plasma, Serum Albumin, S-Nitrosothiols, In Vitro Techniques
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