Reactive oxygen species from NADPH oxidase contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension

Candice D. Fike, James C. Slaughter, Mark R. Kaplowitz, Yongmei Zhang, Judy L. Aschner

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Our main objective was to determine whether reactive oxygen species (ROS), such as superoxide (O2-) and hydrogen peroxide (H 2O2), contribute to altered pulmonary vascular responses in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. The effect of the cell-permeable superoxide dismutase mimetic (SOD; M40403) and/or PEG-catalase (PEG-CAT) on responses to acetylcholine (ACh) was measured in endothelium-intact and denuded pulmonary resistance arteries (PRAs; 90-to-300-μm diameter). To determine whether NADPH oxidase is an enzymatic source of ROS, PRA responses to ACh were measured in the presence and absence of a NADPH oxidase inhibitor, apocynin (APO). A Western blot technique was used to assess expression of the NADPH oxidase subunit, p67phox. A lucigenin-derived chemiluminescence technique was used to measure ROS production stimulated by the NADPH oxidase substrate, NADPH. ACh responses, which were dilation in intact control arteries but constriction in both intact and denuded hypoxic arteries, were diminished by M40403, PEGCAT, the combination of M40403 plus PEG-CAT, as well as by APO. Although total amounts were not different, membrane-associated p67phox was greater in PRAs from hypoxic compared with control piglets. NADPH-stimulated lucigenin luminescence was nearly doubled in PRAs from hypoxic vs. control piglets. We conclude that ROS generated by NADPH oxidase contribute to the aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia.

Original languageEnglish (US)
Pages (from-to)L881-L888
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 1 2008

Keywords

  • Hydrogen peroxide
  • M40401
  • M40403
  • Superoxide
  • Superoxide dismutase
  • p67phox

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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