title: Reactive oxygen species-reducing strategies improve pulmonary arterial responses to nitric oxide in piglets with chronic hypoxia-induced pulmonary hypertension.
abstract: OBJECTIVE
  There are no effective treatments for chronic pulmonary hypertension in infants with cardiopulmonary disorders associated with hypoxia, such as those with chronic lung disease. These patients often have poor or inconsistent pulmonary dilator responses to inhaled nitric oxide (iNO) therapy for unknown reasons. One possible explanation for poor responsiveness to iNO is reduced NO bioavailability caused by interactions between reactive oxygen species (ROS) and NO. Our major aim was to determine if strategies to reduce ROS improve dilator responses to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), in resistance pulmonary arteries (PRAs) from a newborn piglet model of chronic pulmonary hypertension.
  
  
  RESULTS
  The dilation to SNAP was significantly impaired in PRAs from piglets with chronic hypoxia-induced pulmonary hypertension. ROS scavengers, including cell-permeable and impermeable agents to degrade hydrogen peroxide (H(2)O(2)), improved dilation to SNAP in PRAs from chronically hypoxic piglets. Treatment with agents to inhibit nitric oxide synthase and NADPH oxidase, potential enzymatic sources of ROS, also improved dilation to SNAP in PRAs from hypoxic piglets.
  
  
  METHODS
  Our studies are the first to utilize a newborn model of chronic pulmonary hypertension to evaluate the impact of a number of potential therapeutic strategies for ROS removal on responses to exogenous NO in the vessels most relevant to the regulation of pulmonary vascular resistance (PRA).
  
  
  CONCLUSIONS
  Strategies aimed at reducing ROS merit further evaluation and consideration as therapeutic approaches to improve responses to iNO in infants with chronic pulmonary hypertension.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. candice.fike@vanderbilt.edu
authors.forename: Candice D
authors.initials: CD
authors.lastname: Fike
authors.forename: Anna
authors.initials: A
authors.lastname: Dikalova
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.forename: M R
authors.initials: MR
authors.lastname: Kaplowitz
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Judy L
authors.initials: JL
authors.lastname: Aschner
mesh_terms: D000818:Animals; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000209:etiology*; D000860:Hypoxia; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013552:Swine
chemical_list: D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D026423:S-Nitroso-N-Acetylpenicillamine; D002374:Catalase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019255:NADPH Oxidases