Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10738694 | Free Radical Biology and Medicine | 2011 | 8 Pages |
Abstract
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 â HNO2]+). Furthermore, IR signal at 1378 cmâ 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.
Keywords
HMBCHPLC-MSDAFcGMPNORESI-MSSGCNOS1OxyhemoglobinNG-nitro-l-arginine methyl esterODQPGI2SMCHMQCCOXIBMXoxyHbnitroarachidonic acidnuclear magnetic resonance3-isobutyl-1-methylxanthine4,5-diaminofluorescein diacetatecAMPl-NAMECyclic adenosine monophosphatecyclooxygenaseAChAcetylcholineArachidonic acidNitro-fatty acidsInfrared radiationinflammationheteronuclear multiple bond coherenceheteronuclear multiple quantum coherenceELISAEnzyme-linked immunosorbent assayNMRElectron paramagnetic resonanceEPRFree radicalsSmooth muscle cellendothelial nitric oxide synthaseSoluble guanylate cyclaseMass spectrometryElectrospray ionization tandem mass spectrometryHomonuclear correlation spectroscopyMethanolMeOHcyclic guanosine monophosphatenorepinephrinesodium nitroprussideNitric oxideVasorelaxationprostacyclinSNPCOSYCarboxy-PTIO
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Authors
Fabiana Blanco, Ana M. Ferreira, Gloria V. López, LucÃa Bonilla, Mercedes González, Hugo Cerecetto, Andrés Trostchansky, Homero Rubbo,