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

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

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
Volume90
Issue number4
Publication statusPublished - 28-03-2001

Fingerprint

Pulmonary Hypertension
Oxidative Stress
Lung
Xanthine Oxidase
Acetylcysteine
Right Ventricular Hypertrophy
Allopurinol
Hypoxia
Blood Vessels
Antioxidants
phosphatidylcholine hydroperoxide

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Hoshikawa, Y., Ono, S., Suzuki, S., Tanita, T., Chida, M., Song, C., ... Fujimura, S. (2001). Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. Journal of Applied Physiology, 90(4), 1299-1306.
Hoshikawa, Yasushi ; Ono, Sadafumi ; Suzuki, Satoshi ; Tanita, Tatsuo ; Chida, Masayuki ; Song, Chun ; Noda, Masafumi ; Tabata, Toshiharu ; Voelkel, Norbert F. ; Fujimura, Shigefumi. / Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. In: Journal of Applied Physiology. 2001 ; Vol. 90, No. 4. pp. 1299-1306.
@article{fcc7cbc0e23f485393937ac7b9f2726f,
title = "Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia",
abstract = "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.",
author = "Yasushi Hoshikawa and Sadafumi Ono and Satoshi Suzuki and Tatsuo Tanita and Masayuki Chida and Chun Song and Masafumi Noda and Toshiharu Tabata and Voelkel, {Norbert F.} and Shigefumi Fujimura",
year = "2001",
month = "3",
day = "28",
language = "English",
volume = "90",
pages = "1299--1306",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "4",

}

Hoshikawa, Y, Ono, S, Suzuki, S, Tanita, T, Chida, M, Song, C, Noda, M, Tabata, T, Voelkel, NF & Fujimura, S 2001, 'Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia', Journal of Applied Physiology, vol. 90, no. 4, pp. 1299-1306.

Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. / Hoshikawa, Yasushi; Ono, Sadafumi; Suzuki, Satoshi; Tanita, Tatsuo; Chida, Masayuki; Song, Chun; Noda, Masafumi; Tabata, Toshiharu; Voelkel, Norbert F.; Fujimura, Shigefumi.

In: Journal of Applied Physiology, Vol. 90, No. 4, 28.03.2001, p. 1299-1306.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia

AU - Hoshikawa, Yasushi

AU - Ono, Sadafumi

AU - Suzuki, Satoshi

AU - Tanita, Tatsuo

AU - Chida, Masayuki

AU - Song, Chun

AU - Noda, Masafumi

AU - Tabata, Toshiharu

AU - Voelkel, Norbert F.

AU - Fujimura, Shigefumi

PY - 2001/3/28

Y1 - 2001/3/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035100461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035100461&partnerID=8YFLogxK

M3 - Article

C2 - 11247927

AN - SCOPUS:0035100461

VL - 90

SP - 1299

EP - 1306

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 4

ER -