Contribution of oxidative stress to pulmonary hypertension induced by chronic hypoxia

Yasushi Hoshikawa, S. Ono, T. Tanita, T. Sakuma, Masafumi Noda, T. Tabata, S. Ueda, Yugo Ashino, S. Fujimura

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Abstract

Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with media wall thickening of pulmonary arteries in rats. Platelet-activating factor plays an important role in the pulmonary vascular remodeling induced by chronic hypoxia, and reactive oxygen species are involved in tissue injury induced by platelet activating factor. We therefore hypothesized that reactive oxygen species contribute to the pulmonary hypertension induced by chronic hypoxia, and examined the effect of N-acetyl-L-cystein (NAC), a free radical scavenger and the precursor of glutathione sulfhydryl (GSH), on hypoxia-induced pulmonary hypertension. We used a chemiluminescence-HPLC assay to measure the levels of phosphatidylcholine hydroperoxide (PCOOH) in the rat lungs exposed to hypoxia. Three weeks of normobaric hypoxia (FiO2 = O.I) with NAC significantly reduced pulmonary hypertension, right ventricular hypertrophy, and media wall thickening of the pulmonary arteries. NAC had no effect on the hematocrit of normoxic or chronically nomobaric hypoxic rats. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. These results indicate that hypoxia induces oxidative stress in the lung tissue, and that oxidative stress may have a role in the development of pulmonary hypertension induced by chronic hypoxia in rats.

Original languageEnglish
Pages (from-to)1168-1173
Number of pages6
JournalJapanese Journal of Thoracic Diseases
Volume33
Issue number11
Publication statusPublished - 1995 Dec 1

Keywords

  • Hypoxic pulmonary hypertension
  • N-acetyl-L-cysteine (NAC)
  • Oxidative stress
  • Phosphatidylcholinehydroperoxide (PCOOH)
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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  • Cite this

    Hoshikawa, Y., Ono, S., Tanita, T., Sakuma, T., Noda, M., Tabata, T., Ueda, S., Ashino, Y., & Fujimura, S. (1995). Contribution of oxidative stress to pulmonary hypertension induced by chronic hypoxia. Japanese Journal of Thoracic Diseases, 33(11), 1168-1173.