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 
PKCzeta, 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.