Hydrogen sulfide mediates vasoactivity in an O2-dependent manner

Abstract

Hydrogen sulfide (H 2 S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H 2 S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H 2 S include ATP-sensitive K+channels, and H 2 S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O 2 dependent, but this has not been addressed in most studies designed to elucidate the role of H 2 S in vascular function. This is important, since H 2 S reactions can be dramatically altered by the high concentrations of O 2 used in cell culture and organ bath experiments. To test the hypothesis that the effects of H 2 S on the vasculature are O 2 dependent, we have measured real-time levels of H 2 S and O 2 in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H 2 S sensor developed in our laboratory was used to measure H 2 S levels. Here we report that, in rat aorta, H 2 S concentrations that mediate rapid contraction at high O 2 levels cause rapid relaxation at lower physiological O 2 levels. At high O 2, the vasoconstrictive effect of H 2 S suggests that it may not be H 2 S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H 2 S to modulate vascular tone in vivo.