Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response that diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts. This response is important for the local matching of blood perfusion to ventilation and improves pulmonary gas exchange efficiency. HPV is an ancient and highly conserved response, expressed in the respiratory organs of all vertebrates, including lungs of mammals, birds, and reptiles; amphibian skin; and fish gills. The mechanism underlying HPV and how cells sense low PO₂ remains elusive. In perfused trout gills (Oncorhynchus mykiss), acute hypoxia, as well as H₂S, caused an initial and transient constriction of the vasculature. Inhibition of the enzymes cystathionine- β-synthase and cystathionine-γ-lyase, which blocks H₂S production, abolished the hypoxic response. Individually blocking the four complexes in the electron transport chain abolished both the hypoxic and the H₂S-mediated constriction. Glutathione, an antioxidant and scavenger of superoxide, attenuated the vasoconstriction in response to hypoxia and H₂S. Furthermore, diethyldithiocarbamate, an inhibitor of superoxide dismutase, attenuated the hypoxic and H₂S constriction. This strongly suggests that H₂S mediates the hypoxic vasoconstriction in trout gills. H₂S may stimulate the mitochondrial production of superoxide, which is then converted to hydrogen peroxide (H₂O₂). Thus, H₂O₂ may act as the "downstream" signaling molecule in hypoxic vasoconstriction.