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 language | English |
|---|---|
| Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
| Volume | 303 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 1 2012 |
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Keywords
- Gill resistance
- Hypoxia
- Mitochondria
- Oxygen-sensing
- Reactive oxygen species
- Trout
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills. / Skovgaard, Nini; Olson, Kenneth.
In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 303, No. 5, 01.09.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills
AU - Skovgaard, Nini
AU - Olson, Kenneth
PY - 2012/9/1
Y1 - 2012/9/1
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.
KW - Gill resistance
KW - Hypoxia
KW - Mitochondria
KW - Oxygen-sensing
KW - Reactive oxygen species
KW - Trout
UR - http://www.scopus.com/inward/record.url?scp=84865768879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865768879&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00151.2012
DO - 10.1152/ajpregu.00151.2012
M3 - Article
C2 - 22739350
AN - SCOPUS:84865768879
VL - 303
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0193-1857
IS - 5
ER -