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Intermittent Hypoxia Increases Endothelin‐1‐Induced Reactive Oxygen Species Generation through PKC Signaling in Small Pulmonary Arteries
Author(s) -
Snow Jessica,
Gonzalez Bosc Laura V.,
Kanagy Nancy L,
Walker Benjimen R.,
Resta Thomas C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1034.10
Subject(s) - protein kinase c , endothelin 1 , hypoxia (environmental) , reactive oxygen species , endocrinology , medicine , lung , signal transduction , chemistry , basal (medicine) , endothelin receptor , pulmonary hypertension , oxygen , receptor , biochemistry , insulin , organic chemistry
Intermittent hypoxia (IH) augments endothelin‐1 (ET‐1) induced pulmonary vasoconstrictor reactivity through a PKCα/β and reactive oxygen species (ROS)‐dependent mechanism. Although this response may contribute to IH induced pulmonary hypertension, the mechanism by which IH upregulates PKC signaling is unknown as is whether PKC and ROS signal in series to mediate this response. We hypothesized that increased pulmonary arterial PKCα/β expression and activity after IH mediate the ET‐1 induced ROS generation not seen under control conditions. The PKCα/β inhibitor myr‐PKC (10 μM) decreased ET‐1 stimulated ROS levels as measured by dihydroethidium (DHE) fluorescence in endothelium‐disrupted, pressurized pulmonary arteries (~150 μm diameter) from IH rats (3 min cycles; 5% O 2 , 5% CO 2 /air flush; 7 h/day; 4 wk) but not in arteries from sham (air cycled) rats. Although total pulmonary arterial PKCα/β mRNA or protein levels did not differ between groups, basal levels of PKCβI/II were greater in the membrane fraction of IH arteries compared to sham, consistent with elevated PKCβ activity. Therefore IH appears to augment ET‐1 mediated ROS generation in pulmonary arteries through a PKCα/β signaling mechanism independent of altered PKC expression.