Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation.
How vertebrate blood vessels sense acute hypoxia and respond either by constricting (hypoxic vasoconstriction) or dilating (hypoxic vasodilation) has not been resolved. In the present study we compared the mechanical and electrical responses of select blood vessels to hypoxia and H2S, measured vascular H2S production, and evaluated the effects of inhibitors of H2S synthesis and addition of the H2S precursor, cysteine, on hypoxic vasoconstriction and hypoxic vasodilation. We found that: (1) in all vertebrate vessels examined to date, hypoxia and H2S produce temporally and quantitatively identical responses even though the responses vary from constriction (lamprey dorsal aorta; lDA), to dilation (rat aorta; rA), to multi-phasic (rat and bovine pulmonary arteries; rPA and bPA, respectively). (2) The responses of lDA, rA and bPA to hypoxia and H2S appear competitive; in the presence of one stimulus, the response to the other stimulus is substantially or completely eliminated. (3) Hypoxia and H2S produce the same degree of cell depolarization in bPA. (4) H2S is constitutively synthesized by lDA and bPA vascular smooth muscle. (5) Inhibition of H2S synthesis inhibits the hypoxic response of lDA, rA, rPA and bPA. (6) Addition of the H2S precursor, cysteine, doubles hypoxic contraction in lDA, prolongs contraction in bPA and alters the re-oxygenation response of rA. These studies suggest that H2S may serve as an O2 sensor/transducer in the vascular responses to hypoxia. In this model, the concentration of vasoactive H2S in the vessel is governed by the balance between endogenous H2S production and its oxidation by available O2.
Olson
Kenneth R
KR
Indiana University School of Medicine-South Bend, 1234 Notre Dame Avenue, South Bend, IN 46617, USA. kolson@nd.edu
Dombkowski
Ryan A
RA
Russell
Michael J
MJ
Doellman
Meredith M
MM
Head
Sally K
SK
Whitfield
Nathan L
NL
Madden
Jane A
JA
D000818:Animals; D002417:Cattle; D003545:Cysteine / Q000494:pharmacology; D004594:Electrophysiology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D048428:Petromyzon / Q000502:physiology; D051381:Rats; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014714:Vertebrates / Q000502:physiology*
D003545:Cysteine; D010100:Oxygen; D006862:Hydrogen Sulfide