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Role of Reactive Oxygen Species in Kv Channel Inhibition and Vasoconstriction Induced by TP Receptor Activation in Rat Pulmonary Arteries
Author(s) -
COGOLLUDO ANGEL,
FRAZZIANO GIOVANNA,
COBEÑO LAURA,
MORENO LAURA,
LODI FEDERICA,
VILLAMOR EDUARDO,
TAMARGO JUAN,
PEREZVIZCAINO FRANCISCO
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.053
Subject(s) - apocynin , nadph oxidase , catalase , chemistry , reactive oxygen species , hypoxic pulmonary vasoconstriction , thromboxane a2 , superoxide , vasoconstriction , biochemistry , receptor , pharmacology , biophysics , endocrinology , enzyme , biology
Voltage‐gated potassium channels (Kv) and thromboxane A 2 (TXA 2 ) have been involved in several forms of human and experimental pulmonary hypertension. We have reported that the TXA 2 analog U46619, via activation of TP receptors and PKCζ, inhibited Kv currents in rat pulmonary artery smooth muscle cells (PASMC), increased cytosolic calcium, and induced a contractile response in isolated rat and piglet pulmonary arteries (PA). Herein, we have analyzed the role of reactive oxygen species (ROS) in this signaling pathway. In rat PA, U46619 increased dichlorofluorescein fluorescence, an indicator of intracellular hydrogen peroxide, and this effect was prevented by the NADPH oxidase inhibitor apocynin and by polyethyleneglycol‐catalase (PEG‐catalase, a membrane‐permeable form of catalase). U46619 inhibited Kv currents in native PASMC and these effects were strongly inhibited by apocynin. The contractile responses to U46619 in isolated PA were inhibited by PEG‐catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin. A membrane permeable of hydrogen peroxide, t‐butyl hydroperoxide, also inhibited Kv currents and induced a contractile response. Activation of NADPH oxidase and the subsequent production of hydrogen peroxide are involved in the Kv channel inhibition and the contractile response induced by TP receptor activation in rat PA.