The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants
2015
Аутори:
Berenyiova, AndreaGrman, Marian
Mijuskovic, Ana
Stasko, Andrej
Misak, Anton
Nagy, Peter
Ondriasova, Elena
Cacanyiova, Sona
Brezova, Vlasta
Feelisch, Martin
Ondrias, Karol
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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 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.
Кључне речи:
Hydrogen sulfide; Nitric oxide; Nitrosopersulfide; Polysulfides; Aorta relaxation; UterusИзвор:
Nitric Oxide-Biology and Chemistry, 2015, 46, SI, 123-130
DOI: 10.1016/j.niox.2014.12.008
ISSN: 1089-8611