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Intermittent hypoxia increases PKCα/β‐ and reactive oxygen species‐dependent myofilament Ca 2+ sensitization in small pulmonary arteries
Author(s) -
Snow Jessica,
Kanagy Nancy,
Walker Benjimen,
Resta Thomas
Publication year - 2009
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.23.1_supplement.770.6
Subject(s) - sensitization , rottlerin , protein kinase c , tiron , vasoconstriction , reactive oxygen species , hypoxic pulmonary vasoconstriction , chemistry , stimulation , medicine , hypoxia (environmental) , endocrinology , rho associated protein kinase , signal transduction , oxygen , immunology , biochemistry , superoxide , organic chemistry , enzyme
Intermittent hypoxia (IH) elicits pulmonary hypertension, increases circulating levels of the vasoconstrictor peptide, endothelin‐1 (ET‐1), and increases ET‐1‐mediated Ca 2+ sensitization in pulmonary vascular smooth muscle (VSM). We hypothesized that, similar to effects of IH in systemic arteries, IH enhances ET‐1‐induced Ca 2+ sensitization in pulmonary.VSM through stimulation of PKCδ. To test this hypothesis, we assessed vasoconstrictor and VSM Ca 2+ responses to ET‐1 in the presence of the PKCδ inhibitor, rottlerin, or the PKCα/β inhibitor, myr‐PKC(20‐28), in endothelium‐disrupted, pressurized pulmonary arteries (~160 µm inner diameter) from IH or sham rats, as previously reported. In contrast to our hypothesis, rottlerin did not attenuate ET‐1‐mediated vasoconstriction in either group. However, myr‐PKC normalized reactivity between IH and sham groups without altering the associated Ca 2+ responses. Because reactive oxygen species (ROS) contribute to ET‐1‐induced Ca 2+ sensitization after IH, and ROS can activate PKC, we additionally assessed responses to ET‐1 in the presence of both myr‐PKC and the ROS scavenger, tiron. This drug combination inhibited ET‐1‐induced Ca 2+ sensitization in vessels from IH but not sham rats to a similar degree as myr‐PKC or tiron alone. We conclude that IH augments ET‐1‐induced Ca 2+ sensitization via PKCα/β and ROS, which may signal through a common pathway.