Reappraisal of [H.sub.2]S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling

Hydrogen sulfide ([H.sub.2]S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable [H.sub.2]S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 [micro]M, 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 [H.sub.2]S gas and turnover of exogenous [H.sub.2]S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, [H.sub.2]S 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 [H.sub.2]S could transiently increase, we measured oxygen-dependent [H.sub.2]S production by trout hearts in vitro and in vivo. [H.sub.2]S has been shown to mediate ischemic preconditioning (IPC) in mammals. [PC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial [H.sub.2]S production was inversely related to P[O.sub.2], whereas we failed to detect [H.sub.2]S 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.sub.2]S in [PC, i.e., oxygen sensing, but they fail to provide any evidence that [H.sub.2]S signaling is mediated by the circulation. gasotransmitter; hydrogen sulfide metabolism; vascular signaling