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

• Published in: Journal of applied physiology (1985) 2001-04, Vol.90 (4), p.1299-1306
• Main Authors: Hoshikawa, Yasushi, Ono, Sadafumi, Suzuki, Satoshi, Tanita, Tatsuo, Chida, Masayuki, Song, Chun, Noda, Masafumi, Tabata, Toshiharu, Voelkel, Norbert F, Fujimura, Shigefumi
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Allopurinol - pharmacology; Animals; Antioxidants - pharmacology; Biological and medical sciences; Chronic Disease; Enzyme Inhibitors - pharmacology; Hypertension; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Hypertrophy, Right Ventricular - pathology; Hypertrophy, Right Ventricular - physiopathology; Lung - metabolism; Lungs; Male; Medical sciences; Oxidative Stress; Oxygen; Oxygen - metabolism; Oxygen - pharmacology; Phosphatidylcholines - metabolism; Pneumology; Pulmonary Artery - pathology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Rats; Rats, Sprague-Dawley; Tunica Media - pathology; Ventricular Function, Right; Xanthine Oxidase - metabolism
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2001.90.4.1299

1  Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; and 2  Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262 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. N -acetylcysteine; phosphatidylcholine hydroperoxide; xanthine oxidase; allopurinol; pulmonary vascular remodeling