title: Reactive oxygen species scavengers improve voltage-gated K(+) channel function in pulmonary arteries of newborn pigs with progressive hypoxia-induced pulmonary hypertension.
abstract: Abstract Changes in voltage-gated K(+) (Kv) channel function contribute to the pathogenesis of pulmonary hypertension. Yet the mechanisms underlying Kv channel impairments in the pulmonary circulation remain unclear. We tested the hypothesis that reactive oxygen species (ROSs) contribute to the Kv channel dysfunction that develops in resistance-level pulmonary arteries (PRAs) of piglets exposed to chronic in vivo hypoxia. Piglets were raised in either room air (control) or hypoxia for 3 or 10 days. To evaluate Kv channel function, responses to the Kv channel antagonist 4-aminopyridine (4-AP) were measured in cannulated PRAs. To assess the influence of ROSs, PRAs were treated with the ROS-removing agent M40403 (which dismutates superoxide to hydrogen peroxide), plus polyethylene glycol catalase (which converts hydrogen peroxide to water). Responses to 4-AP were diminished in PRAs from both groups of hypoxic piglets. ROS-removing agents had no impact on 4-AP responses in PRAs from piglets exposed to 3 days of hypoxia but significantly increased the response to 4-AP in PRAs from piglets exposed to 10 days of hypoxia. Kv channel function is impaired in PRAs of piglets exposed to 3 or 10 days of in vivo hypoxia. ROSs contribute to Kv channel dysfunction in PRAs from piglets exposed to hypoxia for 10 days but are not involved with the Kv channel dysfunction that develops within 3 days of exposure to hypoxia. Therapies to remove ROSs might improve Kv channel function and thereby ameliorate the progression, but not the onset, of pulmonary hypertension in chronically hypoxic newborn piglets.
authors.affiliation: 1 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
authors.forename: Candice D
authors.initials: CD
authors.lastname: Fike
authors.forename: Judy L
authors.initials: JL
authors.lastname: Aschner
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kaplowitz
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jane A
authors.initials: JA
authors.lastname: Madden