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dc.creatorBerenyiova, Andrea
dc.creatorGrman, Marian
dc.creatorMijuskovic, Ana
dc.creatorStasko, Andrej
dc.creatorMisak, Anton
dc.creatorNagy, Peter
dc.creatorOndriasova, Elena
dc.creatorCacanyiova, Sona
dc.creatorBrezova, Vlasta
dc.creatorFeelisch, Martin
dc.creatorOndrias, Karol
dc.description.abstractThe chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO-) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50 nM), whereas Na2S and polysulfides have little effect at 1-5 mu M. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500 nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10 mu M), and by the NO scavenger cPTIO (100 mu M), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1 mM) or methemoglobin (20 mu M heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500 nM based on the starting material) was inhibited to a lesser extent by ODQ only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD(2))-Fe2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO-, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk. (C) 2014 Elsevier Inc. All rights reserved.
dc.description.sponsorshipSlovak Research and Development Agency {[}APVV-0074-11]; Hungarian National Science Foundation (OTKA) {[}K 109843]; VEGA {[}2/0050/13, 1/0289/12, 2/0074/14]; BMBS COST Action {[}BM1005]; Marie Curie International Reintegration Grant {[}PIRG08-GA-2010-277006]
dc.sourceNitric Oxide-Biology and Chemistry
dc.subjectHydrogen sulfide
dc.subjectNitric oxide
dc.subjectAorta relaxation
dc.titleThe reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants
dcterms.abstractМијусковиц, Aна; Беренyиова, Aндреа; Грман, Мариан; Стаско, Aндреј; Мисак, Aнтон; Нагy, Петер; Ондриасова, Елена; Цацанyиова, Сона; Брезова, Власта; Феелисцх, Мартин; Ондриас, Карол;

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