Nitroxyl Anion Donor, Angeli’s Salt, Does Not Develop Tolerance in Rat Isolated Aortae

Irvine, Jennifer C; Favaloro, Joanne L; Widdop, Robert E; Kemp-Harper, Barbara K

doi:10.1161/01.hyp.0000259328.04159.90

Cited by 102 publications

(115 citation statements)

References 42 publications

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“…These results indicate that a significant portion of the relaxation induced by these reaction products is mediated by an alternative mechanism, which may directly activate sGC without releasing free NO. These effects of cPTIO and ODQ on the products of the Sulfide/GSNO interaction are reminiscent of reports on effects of the HNO donor Angeli's salt (AS) [43][44][45]. This suggests that HNO may be involved in the relaxation effects induced by the 'SSNO -mix'.…”

Section: Modulation Of the Relaxation Effect Of The 'Ssno -Mix' And Gsnomentioning

confidence: 60%

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

et al. 2015

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A B S T R A C TThe 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)-Fe 2+ 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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Section: Modulation Of the Relaxation Effect Of The 'Ssno -Mix' And Gsnomentioning

confidence: 60%

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

et al. 2015

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“…As shown in the figure, NO-induced COX inhibition that was 43% in the absence of uric acid was protected to 71% with 1 mM uric acid. To study potential mechanisms underlying peroxynitrite formation, SOD and L-cysteine, a nitroxyl anion scavenger (11,12) were tested. Figure 2B shows that SOD did not protect the COX inhibition.…”

Section: Resultsmentioning

confidence: 99%

Nitric oxide irreversibly inhibits cytochrome oxidase at low oxygen concentrations: Evidence for inverse oxygen concentration‐dependent peroxynitrite formation

2007

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SummaryThe present study shows that nitric oxide (NO) irreversibly inhibits purified cytochrome oxidase in a reverse oxygen concentration-dependent manner. The inhibition is dramatically protected by a peroxynitrite scavenger, suggesting that peroxynitrite is formed from the reaction of NO with cytochrome oxidase at low oxygen concentration, and that peroxynitrite is involved in irreversible cytochrome oxidase inactivation. Production of nitroxyl anion or superoxide was tested as potential mechanisms underlying the conversion of NO to peroxynitrite. A nitroxyl anion scavenger potently protected the irreversible inhibition, whereas a superoxide dismutase did not provide protective effect, suggesting that the peroxynitrite was formed from nitroxyl anion rather than the reaction of NO with superoxide. IUBMBIUBMB Life, 60(1): [64][65][66][67] 2008

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“…1 HNO may possess some unique and favorable properties, which are relevant in the treatment of cardiovascular disorders such as angina, acute hypertensive crises and atherosclerosis. 1 Some reports confirm that Angeli's salt (an HNO donor) is a potent vasodilator both in vitro and in vivo, which can elicit vasorelaxation in an isolated large conduits, [2][3][4][5] small resistance arteries 6 and intact coronary vessels. 7 In addition, HNO demonstrates distinct actions on myocardial contractile function that differ from NO.…”

Section: Introductionmentioning

confidence: 97%

A near-infrared fluorescent probe for the selective detection of HNO in living cells and in vivo

Liu

Jing

et al. 2015

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Nitroxyl (HNO), the one-electron reduced and protonated analogue of nitric oxide (NO), demonstrates distinctive bio-pharmacological effects in the treatment of cardiovascular disorders. Herein, we design and synthesize a near-infrared (NIR) metal-free fluorescent probe Cyto-JN for the detection of nitroxyl (HNO) in living cells and in vivo. The metal-free Cyto-JN is composed of two moieties: the Aza-BODIPY fluorophore and the HNO recognition unit, the diphenylphosphinobenzoyl group. Cyto-JN can react with HNO in a 1 : 1 stoichiometry, which may bring great benefit to the detection efficiency of bioassays. Cyto-JN shows high sensitivity toward HNO and exhibits low cytotoxic effect on cells. Moreover, the probe displays good selectivity for the detection of HNO in the presence of various biologically related species.Cyto-JN can be applied successfully to bio-imaging of HNO in living cells and in mice. The results of flow cytometry confirm that the probe Cyto-JN can be used to detect intracellular HNO qualitatively and quantitatively.

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Nitroxyl Anion Donor, Angeli’s Salt, Does Not Develop Tolerance in Rat Isolated Aortae

Cited by 102 publications

References 42 publications

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

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

Nitric oxide irreversibly inhibits cytochrome oxidase at low oxygen concentrations: Evidence for inverse oxygen concentration‐dependent peroxynitrite formation

A near-infrared fluorescent probe for the selective detection of HNO in living cells and in vivo

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