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COMPARATIVE AND EVOLUTIONARY PHYSIOLOGY

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

¹Indiana University School of Medicine-South Bend, South Bend; and ²Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana

Submitted 11 January 2008 ; accepted in final form 15 April 2008

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 H₂S 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 PO₂, 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 H₂S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H₂S signaling is mediated by the circulation.

gasotransmitter; hydrogen sulfide metabolism; vascular signaling

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