The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants
The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants
The 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?µM. 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?µM), and by the NO scavenger cPTIO (100?µM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1?mM) or methemoglobin (20?µM 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 (MGD2)-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.
aorta relaxation, hydrogen sulphide, nitric oxide, nitrosopersulfide, polysulfides, uterus
123-130
Berenyiova, Andrea
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Grman, Marian
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Mijuskovic, Ana
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Stasko, Andrej
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Misak, Anton
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Nagy, Peter
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Ondriasova, Elena
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Cacanyiova, Sona
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Brezova, Vlasta
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Feelisch, Martin
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Ondrias, Karol
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Berenyiova, Andrea
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Grman, Marian
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Mijuskovic, Ana
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Stasko, Andrej
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Misak, Anton
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Nagy, Peter
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Ondriasova, Elena
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Cacanyiova, Sona
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Brezova, Vlasta
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Feelisch, Martin
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Ondrias, Karol
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Berenyiova, Andrea, Grman, Marian, Mijuskovic, Ana, Stasko, Andrej, Misak, Anton, Nagy, Peter, Ondriasova, Elena, Cacanyiova, Sona, Brezova, Vlasta, Feelisch, Martin and Ondrias, Karol
(2014)
The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants.
Nitric Oxide, 46, .
(doi:10.1016/j.niox.2014.12.008).
(PMID:25529482)
Abstract
The 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?µM. 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?µM), and by the NO scavenger cPTIO (100?µM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1?mM) or methemoglobin (20?µM 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 (MGD2)-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.
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e-pub ahead of print date: 18 December 2014
Keywords:
aorta relaxation, hydrogen sulphide, nitric oxide, nitrosopersulfide, polysulfides, uterus
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 373161
URI: http://eprints.soton.ac.uk/id/eprint/373161
ISSN: 1089-8603
PURE UUID: 7462584e-1e8b-4333-86f4-9921a3904b81
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Date deposited: 12 Jan 2015 10:52
Last modified: 15 Mar 2024 03:42
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Author:
Andrea Berenyiova
Author:
Marian Grman
Author:
Ana Mijuskovic
Author:
Andrej Stasko
Author:
Anton Misak
Author:
Peter Nagy
Author:
Elena Ondriasova
Author:
Sona Cacanyiova
Author:
Vlasta Brezova
Author:
Karol Ondrias
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