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

Abstract

Hydrogen sulfide (H(2)S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H(2)S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 microM, 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(2)S gas and turnover of exogenous H(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(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(2)S could transiently increase, we measured oxygen-dependent H(2)S production by trout hearts in vitro and in vivo. H(2)S 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 H(2)S production was inversely related to Po(2), whereas we failed to detect H(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(2)S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H(2)S signaling is mediated by the circulation.

Hydrogen sulfide as an oxygen sensor

“…In rat tissues, O 2 either inhibits H 2 S production or it may be associated with H 2 S consumption and both are reversed by hypoxia (30,44). Similar observations have been made in a variety of tissues from numerous vertebrates (32,89,94,126,128,186). A compelling argument for H 2 S-mediated O 2 sensing can be made by comparing bovine and sea lion lungs.…”

Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

“…H 2 S production by homogenized trout intestine was measured in real time using an amperometric (polarographic) H 2 S sensor constructed in the laboratory (Whitfield et al, 2008). Approximately 1g of anterior intestine was homogenized, on ice, in 9ml of Cortland buffered saline and gassed on a rotary tonometer with humidified 100% nitrogen to remove the oxygen.…”

“…Although there are many reports of plasma and blood H 2 S concentration between 30 and 300mmoll -1 , these may be experimental artifacts (reviewed in Olson, 2009). In fact, H 2 S may not even exist in the circulation (Whitfield et al, 2008). Recent measurements have also shown that the concentration of H 2 S in a variety of tissues appears to be well below 1mmoll -1 .…”

“…As described above, we have proposed that O 2 -dependent metabolism of H 2 S serves as an O 2 'sensor' in a variety of mammalian and non-mammalian tissues Olson et al, 2006;Olson et al, 2008a;Olson et al, 2008b;Whitfield et al, 2008) (reviewed in . Our hypothesis is based on the following observations: (1) H 2 S and hypoxia produce essentially identical responses in a variety of tissues, (2) tissues enzymatically generate H 2 S, (3) tissue production of H 2 S, or the concentration of exogenous H 2 S, is inversely related to oxygen availability, i.e.…”

Selective fluorescent probes for live-cell monitoring of sulphide

“…As a result of the technical limitations of available methods 11,12 , H 2 S concentrations spanning 10 5 orders of magnitude have been reported in the literature 13 . Moreover, many of the commonly used methods are not amenable for application in vivo or for analysis of tissue or blood samples.…”