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 H ₂S produce temporally and quantitatively identical responses even though the responses vary from constriction (lamprey dorsal aorta; IDA), to dilation (rat aorta; rA), to multiphasic (rat and bovine pulmonary arteries; rPA and bPA, respectively). (2) The responses of IDA, 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 IDA and bPA vascular smooth muscle. (5) Inhibition of H₂S synthesis inhibits the hypoxic response of IDA, rA, rPA and bPA. (6) Addition of the H₂S precursor, cysteine, doubles hypoxic contraction in IDA, prolongs contraction in bPA and alters the re-oxygenation response of rA. These studies suggest that H ₂S may serve as an O₂ sensor/transducer in the vascular responses to hypoxia. In this model, the concentration of vasoactive H ₂S in the vessel is governed by the balance between endogenous H ₂S production and its oxidation by available O₂.