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Modulation of Ca2+ signalling in human vascular endothelial cells by hydrogen sulfide

  • Claudia C. Bauer
    Affiliations
    Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
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  • John P. Boyle
    Affiliations
    Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
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  • Karen E. Porter
    Affiliations
    Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
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  • Chris Peers
    Correspondence
    Corresponding author at: Division of Cardiovascular and Neuronal Remodelling, Faculty of Medicine and Health, Worsley Building (Level 10), University of Leeds, Clarendon Way, Leeds LS2 9JT, UK. Tel.: +44 1133434174; fax: +44 1133434803.
    Affiliations
    Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
    Search for articles by this author

      Abstract

      Hydrogen sulfide (H2S) is now recognised as an important endogenous antihypertensive molecule and is synthesised in the vasculature primarily by endothelial cystathionine γ lyase. Activity of this enzyme, and the production of other vasoactive substances by the endothelium, are subject to modulation by changes of [Ca2+]i. Here, we have used microfluorimetry to investigate whether H2S can regulate human endothelial [Ca2+]i. H2S (applied via the donor NaHS, 5–500 μM) caused concentration-dependent rises of [Ca2+]i which were attributable to release from an ATP- and 4-CEP sensitive intracellular pool. Rises of [Ca2+]i evoked by H2S were essentially abolished by prior pool depletion. In the absence of external Ca2+, H2S slowed the decay phase of responses to cyclopiazonic acid, but this could not be attributed to the inhibition of Ca2+ extrusion since the effects of H2S were at least additive with the Na+/Ca2+ exchange inhibitors bepridil and SEA 0400 and the Ca2+ ATPase inhibitor, carboxyeosin. In some but not all the cells, re-exposure to extracellular Ca2+ following the addition and removal of H2S activated capacitative Ca2+ entry (CCE), and H2S increased ATP-evoked (but not thapsigargin-evoked) CCE. Effects of H2S were not mediated by energy depletion or production of cyclic ADP ribose. Our data indicate that H2S can modulate endothelial [Ca2+]i via multiple mechanisms, and such effects are likely to contribute to this gasotransmitter's beneficial actions.

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