Free radical biology & medicine, 2011-02, Vol.50 (3), p.411-418
2011
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- Autor(en) / Beteiligte
- Titel
- 6-Methylnitroarachidonate: A novel esterified nitroalkene that potently inhibits platelet aggregation and exerts cGMP-mediated vascular relaxation
- Ist Teil von
- Free radical biology & medicine, 2011-02, Vol.50 (3), p.411-418
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- Nitro-fatty acids represent endogenously occurring products of oxidant-induced nitration reactions. We have previously synthesized a mixture of four isomers of nitroarachidonic acid, a novel anti-inflammatory signaling mediator. In this study, we synthesized and chemically and biologically characterized for the first time an esterified nitroalkene derived from the nitration of methylarachidonate (AAMet): 6-methylnitroarachidonate (6-AAMetNO2). Synthesis was performed by reacting AAMet with sodium nitrite under acidic conditions. Analysis by mass spectrometry (positive-ion ESI-MS) showed an [M+H]+ ion of m/z 364, characteristic of AAMetNO2. Fragmentation of this ion yielded a daughter ion at m/z 317, corresponding to the neutral loss of the nitro group ([M+H−HNO2]+). Furthermore, IR signal at 1378cm−1 and NMR data confirmed the structure of a 6-nitro-positional isomer. This novel esterified nitroalkene was capable of promoting vascular protective actions including: (a) the induction of vasorelaxation via endothelium-independent mechanisms, associated with an increase in smooth muscle cell cGMP levels, and (b) a potent dose-dependent inhibition of human platelet aggregation. We postulate that 6-AAMetNO2 could be a potential drug for the prevention of vascular and inflammatory diseases, and the presence of the methyl group may increase its pharmacological potential.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0891-5849eISSN: 1873-4596DOI: 10.1016/j.freeradbiomed.2010.11.031Titel-ID: cdi_proquest_miscellaneous_847282730
- Format
- –
- Schlagworte
- acids, Animals, Aorta, Thoracic - drug effects, Aorta, Thoracic - physiology, Arachidonic Acids - chemical synthesis, Arachidonic Acids - chemistry, Arachidonic Acids - pharmacology, cGMP, cyclic GMP, Cyclic GMP - metabolism, drugs, electrospray ionization mass spectrometry, Endothelium, Vascular - drug effects, Endothelium, Vascular - physiology, esterification, Free radicals, Humans, In Vitro Techniques, Inflammation, isomers, Lipid nitration, Male, Methylnitroarachidonate, Muscle, Smooth, Vascular - drug effects, Muscle, Smooth, Vascular - physiology, Nitric oxide, Nitric Oxide - metabolism, Nitric Oxide Donors - chemical synthesis, Nitric Oxide Donors - chemistry, Nitric Oxide Donors - pharmacology, Nitro-fatty acids, Nitroarachidonic acid, nuclear magnetic resonance spectroscopy, platelet aggregation, Platelet Aggregation Inhibitors - chemical synthesis, Platelet Aggregation Inhibitors - chemistry, Platelet Aggregation Inhibitors - pharmacology, Rats, Rats, Inbred WKY, smooth muscle, sodium nitrite, vasodilation, Vasodilation - drug effects, Vasodilator Agents - chemical synthesis, Vasodilator Agents - chemistry, Vasodilator Agents - pharmacology, Vasorelaxation