Hydrogen sulfide mediates vasoactivity in an O2-dependent manner

Jeffrey R. Koenitzer, T. Scott Isbell, Hetal D. Patel, Gloria A. Benavides, Dale A. Dickinson, Rakesh P. Patel, Victor M. Darley-Usmar, Jack R. Lancaster, Jeannette E. Doeller, David W. Kraus

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146 Scopus citations

Abstract

Hydrogen sulfide (H2S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H2S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H2S include ATP-sensitive K+ channels, and H2S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O2 dependent, but this has not been addressed in most studies designed to elucidate the role of H2S in vascular function. This is important, since H2S reactions can be dramatically altered by the high concentrations of O2 used in cell culture and organ bath experiments. To test the hypothesis that the effects of H2S on the vasculature are O2 dependent, we have measured real-time levels of H2S and O2 in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H 2S sensor developed in our laboratory was used to measure H 2S levels. Here we report that, in rat aorta, H2S concentrations that mediate rapid contraction at high O2 levels cause rapid relaxation at lower physiological O2 levels. At high O 2, the vasoconstrictive effect of H2S suggests that it may not be H2S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H2S to modulate vascular tone in vivo.

Original languageEnglish
Pages (from-to)H1953-H1960
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Aorta
  • Mitochondria
  • Oxygen consumption
  • Sulfide sensor
  • Vasorelaxation

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