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

Nini Skovgaard, Kenneth Olson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number5
DOIs
StatePublished - Sep 1 2012

Fingerprint

Hydrogen Sulfide
Trout
Vasoconstriction
Lung
Cystathionine
Constriction
Superoxides
Pulmonary Gas Exchange
Ditiocarb
Lyases
Reptiles
Oncorhynchus mykiss
Amphibians
Electron Transport
Hydrogen Peroxide
Superoxide Dismutase
Birds
Glutathione
Ventilation
Vertebrates

Keywords

  • Gill resistance
  • Hypoxia
  • Mitochondria
  • Oxygen-sensing
  • Reactive oxygen species
  • Trout

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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N2 - 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.

AB - 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.

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