Hydrogen sulfide mediates vasoactivity in an O2-dependent manner

Abstract

Hydrogen sulfide (H₂S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H₂S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H₂S include ATP-sensitive K⁺channels, and H₂S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O₂dependent, but this has not been addressed in most studies designed to elucidate the role of H₂S in vascular function. This is important, since H₂S reactions can be dramatically altered by the high concentrations of O₂used in cell culture and organ bath experiments. To test the hypothesis that the effects of H₂S on the vasculature are O₂dependent, we have measured real-time levels of H₂S and O₂in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H₂S sensor developed in our laboratory was used to measure H₂S levels. Here we report that, in rat aorta, H₂S concentrations that mediate rapid contraction at high O₂levels cause rapid relaxation at lower physiological O₂levels. At high O₂, the vasoconstrictive effect of H₂S suggests that it may not be H₂S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H₂S to modulate vascular tone in vivo.