RT Journal Article
SR Electronic
T1 Vicinal Nitrohydroxyeicosatrienoic Acids: Vasodilator Lipids Formed by Reaction of Nitrogen Dioxide with Arachidonic Acid
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 611
OP 619
VO 299
IS 2
A1 Michael Balazy
A1 Takafumi Iesaki
A1 James L. Park
A1 Houli Jiang
A1 Pawel M. Kaminski
A1 Michael S. Wolin
YR 2001
UL http://jpet.aspetjournals.org/content/299/2/611.abstract
AB Nitric oxide (NO)-derived species could potentially react with arachidonic acid to generate novel vasoactive metabolites. We studied the reaction of arachidonic acid with nitrogen dioxide (NO2), a free radical that originates from NO oxidation. The reaction mixture contained lipid products that relaxed endothelium-removed bovine coronary arteries. Relaxation to the lipid mixture was inhibited ∼20% by indomethacin and ∼70% by a soluble guanylate cyclase (sGC) inhibitor (ODQ). Thus, novel lipid products, which activate sGC presumably through a mechanism involving NO, appeared to have contributed to the observed vasorelaxation. Lipids that eluted at 9 to 12 min during high-performance liquid chromatography fractionation accounted for about one-half of the vasodilator activity in the reaction mixture, which was inhibited by ODQ. Lipid products in fractions 9 to 12 were identified by electrospray tandem mass spectrometry to be eight isomers having molecular weight of 367 and a fragmentation pattern indicative of arachidonic acid derivatives containing nitro and hydroxy groups and consistent with the structures of vicinal nitrohydroxyeicosatrienoic acids. These lipids spontaneously released NO (183 ± 12 nmol NO/15 min/μmol) as detected by head space/chemiluminescence analysis. Mild alkaline hydrolysis of total lipids extracted from bovine cardiac muscle followed by isotopic dilution gas chromatography/mass spectrometry analysis detected basal levels of nitrohydroxyeicosatrienoic acids (6.8 ± 2.6 ng/g tissue;n = 4). Thus, the oxidation product of NO, NO2, reacts with arachidonic acid to generate biologically active vicinal nitrohydroxyeicosatrienoic acids, which may be important endogenous mediators of vascular relaxation and sGC activation. The American Society for Pharmacology and Experimental Therapeutics