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Cited by 110Nitric Oxide and Endothelin EffectsEicosanoids and Hypertension PharmacologyAntioxidant Activity and Oxidative Stress

Nitrolinoleate, a nitric oxide-derived mediator of cell function: Synthesis, characterization, and vasomotor activity

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Lim, Dong Gun, Sweeney, Scott, Bloodsworth, Allison, White, C. Roger, Chumley, Phillip H., Krishna, N. Rama, Schopfer, Francisco, O'Donnell, Valerie B. +2 more·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.232409599PMC PMC138544
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Abstract

Nitric oxide ( • NO) and • NO-derived reactive species rapidly react with lipids during both autocatalytic and enzymatic oxidation reactions to yield nitrated derivatives that serve as cell signaling molecules. Herein we report the synthesis, purification, characterization, and bioactivity of nitrolinoleate (LNO 2 ). Nitroselenylation of linoleic acid yielded LNO 2 that was purified by solvent extraction, silicic acid chromatography, and reverse-phase HPLC. Structural characterization was performed by IR spectroscopy, 15 N-NMR, LC-negative ion electrospray mass spectroscopy (MS), and chemiluminescent nitrogen analysis. Quantitative MS analysis of cell and vessel LNO 2 metabolism, using L[ 15 N]O 2 as an internal standard, revealed that LNO 2 is rapidly metabolized by rat aortic smooth muscle (RASM) monolayers and rat thoracic aorta, resulting in nitrite production and up to 3-fold increases in cGMP (ED 50 = 30 μM for RASM, 50 μM for aorta). LNO 2 induced endothelium-independent relaxation of preconstricted rat aortic rings, which was unaffected by L G -nitro- l -arginine methyl ester addition and inhibited by the guanylate cyclase inhibitor 1 H -[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one and the • NO scavenger HbO 2 . These results reveal that synthetic LNO 2 , identical to lipid derivatives produced biologically by the reaction of • NO and • NO-derived species with oxidizing unsaturated fatty acids (e.g., linoleate), can transduce vascular signaling actions of • NO.

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  • OA-NO2 exerts vasorelaxation of preconstricted aortic rings.

    “In the context of the vasculature, OA-NO2 inhibits neointimal hyperplasia19 and exerts vasorelaxation of preconstricted aortic rings20.”

    From Nitro-oleic acid inhibits angiotensin II-induced hypertension (2010) · cites this paper as [20]

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Authors
Lim, D. G., Sweeney, S., Bloodsworth, A., White, C. R., Chumley, P. H., Krishna, N. R., Schopfer, F., O'Donnell, V. B., Eiserich, J. P., & Freeman, B. A.
Affiliations
  • University of Alabama at Birmingham (US)
  • Departments of Anesthesiology, Biochemistry and Molecular Genetics, Medicine, and UAB Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35233; Department of Medical Biochemistry, University of Wales Europe College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom; and Department of Medicine, University of California, Davis, CA 95616 USA
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-11-20
Volume
99
Issue
25
Pages
15941-15946
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.232409599
PMC
PMC138544
OpenAlex
W2086506907
Cited by
110
References
64
Citations by year
2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 2 · 2013: 5
FWCI
3.80
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • National Institutes of Health (5p60hl058418-05)
  • National Heart, Lung, and Blood Institute (R01HL64937, R01HL064937, P6-HL-58418, R01HL058115, R01-HL-58115)
  • National Cancer Institute (CA-13 148, P30CA013148)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
nitric oxide, linoleic acid, nitrite production, cyclic GMP, guanylate cyclase, aortic smooth muscle, endothelium-independent relaxation, vasomotor activity, nitric oxide signaling
MeSH terms
Animals, Aorta, Thoracic, Chromatography, High Pressure Liquid, Endothelium, Vascular, Enzyme Inhibitors, Fatty Acids, Unsaturated, Cyclic GMP, Guanylate Cyclase, Inflammation, Linoleic Acids, Muscle, Smooth, Vascular, Nitric Oxide, Nitrites, Nitro Compounds, Oxadiazoles, Oxidation-Reduction, Oxyhemoglobins, Quinoxalines, Spectrophotometry, Infrared, Vasodilation, Free Radical Scavengers, NG-Nitroarginine Methyl Ester, Spectrometry, Mass, Electrospray Ionization, Rats

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