NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets

Kathleen E. Dennis, Judy L. Aschner, D. Milatovic, J. W. Schmidt, Michael Aschner, M. R. Kaplowitz, Y. Zhang, Candice D. Fike

Research output: Contribution to journalArticle

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Abstract

Recently, we reported that reactive oxygen species (ROS) generated by NADPH oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries (PRAs) of piglets exposed to 3 days of hypoxia (Am J Physiol Lung Cell Mol Physiol 295: L881-L888, 2008). An objective of the present study was to determine whether NOX-derived ROS also contribute to altered PRA responses at a more advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further wished to advance knowledge about the specific NOX and antioxidant enzymes that are altered at early and later stages of pulmonary hypertension. Piglets were raised in room air (control) or hypoxia for 3 or 10 days. Using a cannulated artery technique, we found that treatments with agents that inhibit NOX (apocynin) or remove ROS [an SOD mimetic (M40403) + polyethylene glycol-catalase] diminished responses to ACh in PRAs from piglets exposed to 10 days of hypoxia. Western blot analysis showed an increase in expression of NOX1 and the membrane fraction of p67phox. Expression of NOX4, SOD2, and catalase were unchanged, whereas expression of SOD1 was reduced, in arteries from piglets raised in hypoxia for 3 or 10 days. Markers of oxidant stress, F 2-isoprostanes, measured by gas chromatography-mass spectrometry, were increased in PRAs from piglets raised in hypoxia for 3 days, but not 10 days. We conclude that ROS derived from some, but not all, NOX family members, as well as alterations in the antioxidant enzyme SOD1, contribute to aberrant PRA responses at an early and a more progressive stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume297
Issue number4
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

NADPH Oxidase
Pulmonary Hypertension
Reactive Oxygen Species
Pulmonary Artery
Arteries
Antioxidants
Isoprostanes
Enzymes
Hypoxia
Oxidants
Catalase
Gas Chromatography-Mass Spectrometry
Western Blotting
Air
Newborn Infant
Lung
Membranes

Keywords

  • Catalase
  • F -isoprostanes
  • M40403
  • NOX1
  • NOX4
  • p67phox
  • SOD1
  • SOD2
  • Superoxide dismutase enzymes

ASJC Scopus subject areas

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

Cite this

NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets. / Dennis, Kathleen E.; Aschner, Judy L.; Milatovic, D.; Schmidt, J. W.; Aschner, Michael; Kaplowitz, M. R.; Zhang, Y.; Fike, Candice D.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 297, No. 4, 2009.

Research output: Contribution to journalArticle

Dennis, Kathleen E. ; Aschner, Judy L. ; Milatovic, D. ; Schmidt, J. W. ; Aschner, Michael ; Kaplowitz, M. R. ; Zhang, Y. ; Fike, Candice D. / NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2009 ; Vol. 297, No. 4.
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AU - Schmidt, J. W.

AU - Aschner, Michael

AU - Kaplowitz, M. R.

AU - Zhang, Y.

AU - Fike, Candice D.

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