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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 387, Issue 1, pp 67–74 | Cite as

Hydrogen sulfide protects endothelial nitric oxide function under conditions of acute oxidative stress in vitro.

  • Mohammad R. Al-Magableh
  • Barbara K. Kemp-Harper
  • Hooi H. Ng
  • Alyson A. Miller
  • Joanne L. HartEmail author
Original Article

Abstract

The aim of this study was to examine the ability of H2S, released from NaHS to protect vascular endothelial function under conditions of acute oxidative stress by scavenging superoxide anions (O2 ) and suppressing vascular superoxide anion production. O2 was generated in Krebs' solution by reacting hypoxanthine with xanthine oxidase (Hx-XO) or with the O2 generator pyrogallol to model acute oxidative stress in vitro. O2 generation was measured by lucigenin-enhanced chemiluminescence. Functional responses in mouse aortic rings were assessed using a small vessel myograph. NaHS scavenged O2 in a concentration-dependent manner. Isolated aortic rings exposed to either Hx-XO or pyrogallol displayed significantly attenuated maximum vasorelaxation responses to the endothelium-dependent vasodilator acetylcholine, and significantly reduced NO bioavailability, which was completely reversed if vessels were pre-incubated with NaHS (100 μM). NADPH-stimulated aortic O2 production was significantly attenuated by the NADPH oxidase inhibitor diphenyl iodonium. Prior treatment of vessels with NaHS (100 nM–100 μM; 30 min) inhibited NADPH-stimulated aortic O2 production in a concentration-dependent manner. This effect persisted when NaHS was washed out prior to measuring NADPH-stimulated O2 production. These data show for the first time that NaHS directly scavenges O2 and suppresses vascular NADPH oxidase-derived O2 production in vitro. Furthermore, these properties protect endothelial function and NO bioavailability in an in vitro model of acute oxidative stress. These results suggest that H2S can elicit vasoprotection by both scavenging O2 and by reducing vascular NADPH oxidase-derived O2 production.

Keywords

Hydrogen sulfide Superoxide Vasoprotection NADPH oxidase 

List of abbreviations

DPI

Diphenyl iodonium

Hx-XO

Combination of hypoxanthine and xanthine oxidase

l-NAME

Nω-nitro-l-arginine methyl ester hydrochloride

NADPH

Nicotinamide adenine dinucleotide phosphate

PG

Pyrogallol

ROS

Reactive oxygen species

SOD

Superoxide dismutase

Notes

Acknowledgments

Dr Hart was a NHMRC Peter Doherty Fellow and the project was additionally funded by the William Buckland Foundation, ANZ Trustees and the Ramaciotti Foundation. Dr Miller is the recipient of a NHMRC Career Development Fellowship.

Author disclosure statement

No competing financial interests exist.

Supplementary material

210_2013_920_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mohammad R. Al-Magableh
    • 1
  • Barbara K. Kemp-Harper
    • 1
  • Hooi H. Ng
    • 2
  • Alyson A. Miller
    • 1
  • Joanne L. Hart
    • 2
    Email author
  1. 1.Department of PharmacologyMonash UniversityClaytonAustralia
  2. 2.School of Medical Sciences and Health Innovations Research Institute (HIRi)RMIT UniversityBundoora WestAustralia

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