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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 H25 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. [ABSTRACT FROM AUTHOR]

Hypoxic pulmonary vasoconstriction (HVC), an intrinsic and assumed ubiquitous response of mammalian pulmonary blood vessels, matches regional ventilation to perfusion via an unknown O(2)-sensing mechanism. Global pulmonary hypoxia experienced by individuals suffering from chronic obstructive pulmonary disease or numerous hypoventilation syndromes, including sleep apnea, often produces maladaptive pulmonary hypertension, but pulmonary hypertension is not observed in diving mammals, where profound hypoxia is routine. Here we examined the response of cow and sea lion pulmonary arteries (PA) to hypoxia and observed the expected HVC in the former and a unique hypoxic vasodilation in resistance vessels in the latter. We then used this disparate response to examine the O(2)-sensing mechanism. In both animals, exogenous H(2)S mimicked the vasoactive effects of hypoxia in isolated PA. H(2)S-synthesizing enzymes, cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfur transferase, were identified in lung tissue from both animals by one-dimensional Western blot analysis and immunohistochemistry. The relationship between H(2)S production/consumption and O(2) was examined in real time by use of amperometric H(2)S and O(2) sensors. H(2)S was produced by sea lion and cow lung homogenate in the absence of O(2), but it was rapidly consumed when O(2) was present. Furthermore, consumption of exogenous H(2)S by cow lung homogenate, PA smooth muscle cells, and heart mitochondria was O(2) dependent and exhibited maximal sensitivity at physiologically relevant Po(2) levels. These studies show that HVC is not an intrinsic property of PA and provide further evidence for O(2)-dependent H(2)S metabolism in O(2) sensing.