Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia

Yasushi Hoshikawa, Sadafumi Ono, Satoshi Suzuki, Tatsuo Tanita, Masayuki Chida, Chun Song, Masafumi Noda, Toshiharu Tabata, Norbert F. Voelkel, Shigefumi Fujimura

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204 Citations (Scopus)


Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling. Because hypoxia might promote generation of oxidative stress in vivo, we hypothesized that oxidative stress may play a role in the hypoxia-induced cardiopulmonary changes and examined the effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine oxidase (XO) activity was elevated from day 1 through day 21, especially during the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary hypertension, and allopurinol treatment only for the initial 3 days also reduced the hypoxia-induced right ventricular hypertrophy and pulmonary vascular thickening. These results suggest that oxidative stress produced by activated XO in the induction phase of hypoxic exposure contributes to the development of chronic hypoxic pulmonary hypertension.

Original languageEnglish
Pages (from-to)1299-1306
Number of pages8
JournalJournal of Applied Physiology
Issue number4
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine


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