Skip to main content


  • Meeting abstract
  • Open Access

Nitrosopersulfide (SSNO-) targets soluble guanylyl cyclase and induces vasodilation in vivo

  • 1Email author,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 7,
  • 5,
  • 8,
  • 3,
  • 1,
  • 9 and
  • 4
BMC Pharmacology and Toxicology201516 (Suppl 1) :A42

  • Published:


  • Nitric Oxide
  • Sulfide
  • Thiol
  • Hydrogen Sulfide
  • Aortic Ring


Recent experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide signaling pathways are intimately intertwined particularly in the vasculature, with mutual attenuation or potentiation of biological responses under control of the soluble guanylyl cyclase (sGC) / phopshodiesterase (PDE) pathway. There is now compelling evidence that part of the NO/sulfide cross talk has a chemical foundation via the formation of S/N-hybrid molecules including thionitrous acid (HSNO) and nitrosopersulfde (SSNO-). The aim of this study was to characterize the bioactive products of the interaction between sulfide and NO metabolites targeting sGC that may potentially regulate vasodilation.


We found that the chemical interaction of sulfide with NO or nitrosothiols leads to formation of S/N-hybrid metabolites including SSNO- via intermediate formation of HSNO. Contrary to a recent report in the literature but consistent with the transient nature of HSNO, its formation was not detectable by high-resolution mass spectrometry under physiologically relevant conditions. SSNO- is also formed in non-aqueous media by the reaction of nitrite with oxidized sulfur species including colloidal sulfur and polysulfides. SSNO- is stable in the presence of high concentrations of thiols, release NO, and activates sGC in RFL-6 cells in an NO-dependent fashion. Moreover, SSNO- is a potent vasodilator in aortic rings in vitro and lowers blood pressure in rats in vivo. The presence of high concentrations of SOD or thiols does not affect SSNO- mediated sGC activation, while it potentiates and inhibits the effects of the nitroxyl (HNO) donor Angeli's salt, suggesting that HNO release from SSNO- is not involved in sGC activation.


The reaction between NO and sulfide leads to fomation of S/N-hybrid molecules including SSNO-, releasing NO, activating sGC and inducing vasodilation. SSNO- is considerably more stable than HSNO at pH 7.4 and thus a more likely biological mediator that can account for the chemical cross-talk between NO and sulfide.

Authors’ Affiliations

Cardiovascular Research Laboratory, Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf, Universitätstrasse 1, 40225 Düsseldorf, Germany
Department of Nutrition, University of Reading, Whiteknights, Reading, RG6 6AP, UK
Bloomsbury Institute of Intensive Care Medicine, University College London, Gower Street, London, WC1E 6BT, UK
Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
Center for Molecular Medicine, Slovak Academy of Sciences, Vlarska 7, 83101 Bratislava, Slovakia
Department of Chemistry, Warwick University, Coventry, CV4 7AL, UK
Bruker UK Ltd., Banner Lane, Coventry, CV4 9GH, UK
Department of Molecular Immunology and Toxicology, National Institute of Oncology, Ráth György utca 7-9, 1122 Budapest, Hungary
Medical School, University of St-Andrews, St-Andrews, Fife, KY16 9AJ, Scotland, UK


© Cortese-Krott et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.