Hydrogen sulfide mediates vasoactivity in an O2-dependent manner.
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.
Koenitzer
Jeffrey R
JR
Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
Isbell
T Scott
TS
Patel
Hetal D
HD
Benavides
Gloria A
GA
Dickinson
Dale A
DA
Patel
Rakesh P
RP
Darley-Usmar
Victor M
VM
Lancaster
Jack R
JR
Doeller
Jeannette E
JE
Kraus
David W
DW
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D005260:Female; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D010100:Oxygen; D006862:Hydrogen Sulfide