Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 303, Issue 5, Pages R487-R494Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00151.2012
Keywords
oxygen-sensing; hypoxia; mitochondria; reactive oxygen species; trout; gill resistance
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Funding
- Danish Research Council
- National Science Foundation
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1051627] Funding Source: National Science Foundation
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Skovgaard N, Olson KR. Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills. Am J Physiol Regul Integr Comp Physiol 303: R487-R494, 2012. First published June 27, 2012; doi:10.1152/ajpregu.00151.2012.-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 Po-2 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-beta-synthase and cystathionine-gamma-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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