Generation of oxidative stress contributes to the development of pulmonary
hypertension induced by hypoxia.
Hoshikawa, Yasushi, Sadafumi Ono, Satoshi Suzuki, Tatsuo Tanita, Masayuki Chida,
Chun Song, Masafumi Noda, Toshiharu Tabata, Norbert F. Voelkel, and Shigefumi
Fujimura.
1Department of Thoracic Surgery, Institute of Development, Aging and Cancer,
Tohoku University, Sendai, 980«hyphen»8575, Japan; and 2Division of Pulmonary
Sciences and Critical Care Medicine, University of Colorado Health Sciences Center,
Denver, Colorado 80262
APStracts 8:0023A, 2001.
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.
Received 9 November 2000; accepted in final form 22 November 2000
APS Manuscript Number A0996-0.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 January 2001