Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling

Nathan L. Whitfield, Edward L. Kreimier, Francys C. Verdial, Nini Skovgaard, Kenneth R. Olson

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264 Scopus citations


Hydrogen sulfide (H2S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H2S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 μM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H2S gas and turnover of exogenous H 2S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H2S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H2S could transiently increase, we measured oxygen-dependent H2S production by trout hearts in vitro and in vivo. H2S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H2S production was inversely related to PO 2, whereas we failed to detect H2S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H 2S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H2S signaling is mediated by the circulation.

Original languageEnglish (US)
Pages (from-to)R1930-R1937
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6
StatePublished - Jun 2008


  • Gasotransmitter
  • Hydrogen sulfide metabolism
  • Vascular signaling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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