Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries

J. Q. Liu, J. S.K. Sham, L. A. Shimoda, P. Kuppusamy, J. T. Sylvester

Research output: Contribution to journalArticle

Abstract

To determine whether reactive oxygen species (ROS) play an essential role in hypoxic pulmonary vasoconstriction (HPV) and the cellular locus of ROS production and action during HPV, we measured internal diameter (ID) at constant transmural pressure, lucigenin-derived chemiluminescence (LDCL), and electron paramagnetic resonance (EPR) spin adduct spectra in small distal porcine pulmonary arteries, and dichlorofluorescein (DCF) fluorescence in myocytes isolated from these arteries. Hypoxia (4% O2) decreased ID, increased DCF fluorescence, tended to increase LDCL, and in some preparations produced EPR spectra consistent with hydroxyl and alkyl radicals. Superoxide dismutase (SOD, 150 U/ml) or SOD + catalase (CAT, 200 U/ml) did not alter ID during normoxia but reduced or abolished the constriction induced by hypoxia. SOD also blocked HPV in endothelium-denuded arteries after restoration of the response by exposure to 10-10 M endothelin-1. Confocal fluorescence microscopy demonstrated that labeled SOD and CAT entered pulmonary arterial myocytes. SOD, SOD + CAT, and CAT blocked the increase in DCF fluorescence induced by hypoxia, but SOD + CAT and CAT also caused a stable increase in fluorescence during normoxia, suggesting that CAT diminished efflux of DCF from cells or oxidized the dye directly. We conclude that HPV required increased concentrations of ROS produced by and acting on pulmonary arterial smooth muscle rather than endothelium.

Original languageEnglish (US)
Pages (from-to)L322-L333
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number2 29-2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Catalase
  • Dichlorofluorescein
  • Electron paramagnetic resonance
  • Endothelium
  • Lucigenin
  • Superoxide dismutase
  • Vascular smooth muscle

ASJC Scopus subject areas

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

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