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The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

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
1089-8603
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
de23c111-ed60-4e41-88f3-fd1302b55104
Nagy, Peter
1c1ec453-5922-4e81-ad91-759d512472b7
Ondriasova, Elena
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Cacanyiova, Sona
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Brezova, Vlasta
9b49cabd-238b-46a5-b07a-364e026d3574
Feelisch, Martin
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Ondrias, Karol
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Berenyiova, Andrea
032b7e5c-3288-47b8-965e-0f379099d69d
Grman, Marian
0311d132-fea8-4c83-8220-e48eab83fd17
Mijuskovic, Ana
d5ad6548-5369-4b2a-8b23-d5aed4e68aa1
Stasko, Andrej
849d6e6d-5122-4b4d-882e-c55aa2b9e187
Misak, Anton
de23c111-ed60-4e41-88f3-fd1302b55104
Nagy, Peter
1c1ec453-5922-4e81-ad91-759d512472b7
Ondriasova, Elena
02401d0c-e961-4091-aaed-22a054def3d1
Cacanyiova, Sona
26a4eab1-becb-4088-8788-6bfb9700c1d9
Brezova, Vlasta
9b49cabd-238b-46a5-b07a-364e026d3574
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Ondrias, Karol
1aee74c2-e6e8-4a3f-8662-904ca384bfc5

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, 123-130. (doi:10.1016/j.niox.2014.12.008). (PMID:25529482)

Record type: Article

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: https://eprints.soton.ac.uk/id/eprint/373161
ISSN: 1089-8603
PURE UUID: 7462584e-1e8b-4333-86f4-9921a3904b81
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 12 Jan 2015 10:52
Last modified: 24 Sep 2019 00:39

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Contributors

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: Martin Feelisch ORCID iD
Author: Karol Ondrias

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