Reactive oxygen species (ROS) scavengers improve voltage gated K+ channel (Kv) function in resistance pulmonary arteries of piglets with chronic hypoxia‐induced pulmonary hypertension

Abstract

Kv channels contribute to resting pulmonary vascular tone. ROS have been shown to impair Kv function in a number of vascular beds. Our objective was to determine if Kv channel function is impaired in PRAs of piglets with chronic hypoxia-induced pulmonary hypertension and the role, if any, of ROS in Kv channel dysfunction. Newborn pigs were kept in room air (C) or 11% O2 (H) for 10 days. Cannulated PRA, 100–300 μm, were used to measure responses to the Kv channel antagonist, 4-aminopyridine (4-AP). The role of ROS was evaluated by treating some PRA with an agent that inhibits NADPH oxidase (apocynin) or with agents to remove ROS (the superoxide dismutase mimetic, M40403, plus polyethylene glycol (PEG)-catalase). An immunoblot technique was used to measure Kv1.5 and Kv1.2 amounts in PRA homogenates. The magnitude of constriction to 4-AP was less in PRA from H than C. Treatment with apocynin or with M40403 plus PEG-Catalase improved responses to 4-AP in PRA from H. Kv1.2 abundance was reduced but Kv1.5 abundance was unchanged in PRA from H. Thus, 4-AP sensitive K+ channel function is impaired by 10 days of chronic hypoxia, is associated with reduced Kv 1.2 expression and can be improved by ROS removing agents. ROS derived from NADPH oxidase may underlie, at least in part, impaired Kv channel function in PRA and thereby contribute to the pathogenesis of chronic hypoxia-induced pulmonary hypertension in newborns. Supported by HL68572