Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2

Tetsuya Adachi; Kazunobu Ishikawa; Wataru Hida; Hayato Matsumoto; Takayuki Masuda; Fumiko Date; Kazuhiro Ogawa; Kazuhisa Takeda; Kazumichi Furuyama; Yongzhao Zhang; Tomomi Kitamuro; Hiromasa Ogawa; Yukio Maruyama; Shigeki Shibahara

doi:10.1016/j.bbrc.2004.05.195

Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2

Tetsuya Adachi, Kazunobu Ishikawa, Wataru Hida, Hayato Matsumoto, Takayuki Masuda, Fumiko Date, Kazuhiro Ogawa, Kazuhisa Takeda, Kazumichi Furuyama, Yongzhao Zhang, Tomomi Kitamuro, Hiromasa Ogawa, Yukio Maruyama, Shigeki Shibahara

Center for Environmental Conservation and Research Safety

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73 Citations (Scopus)

Abstract

Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2^-/-) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2^-/- mice also show attenuated ventilatory responses to hypoxia (10% O₂) with normal responses to hypercapnia (10% CO ₂), suggesting the impaired oxygen sensing. Importantly, HO-2 ^-/- mice exhibit normal breathing patterns with normal arterial CO₂ tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.

Original language	English
Pages (from-to)	514-522
Number of pages	9
Journal	Biochemical and biophysical research communications
Volume	320
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2004.05.195
Publication status	Published - 2004 Jul 23

Keywords

Airway chemoreceptor
Carotid body
Heme oxygenase
Hypoxia
Lung
Oxygen
Pulmonary vein
Respiration
Ventilation-perfusion matching

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2004.05.195

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Adachi, T., Ishikawa, K., Hida, W., Matsumoto, H., Masuda, T., Date, F., Ogawa, K., Takeda, K., Furuyama, K., Zhang, Y., Kitamuro, T., Ogawa, H., Maruyama, Y., & Shibahara, S. (2004). Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2. Biochemical and biophysical research communications, 320(2), 514-522. https://doi.org/10.1016/j.bbrc.2004.05.195

Adachi, T, Ishikawa, K, Hida, W, Matsumoto, H, Masuda, T, Date, F, Ogawa, K, Takeda, K, Furuyama, K, Zhang, Y, Kitamuro, T, Ogawa, H, Maruyama, Y & Shibahara, S 2004, 'Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2', Biochemical and biophysical research communications, vol. 320, no. 2, pp. 514-522. https://doi.org/10.1016/j.bbrc.2004.05.195

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title = "Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2",

abstract = "Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2-/-) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2-/- mice also show attenuated ventilatory responses to hypoxia (10% O2) with normal responses to hypercapnia (10% CO 2), suggesting the impaired oxygen sensing. Importantly, HO-2 -/- mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.",

keywords = "Airway chemoreceptor, Carotid body, Heme oxygenase, Hypoxia, Lung, Oxygen, Pulmonary vein, Respiration, Ventilation-perfusion matching",

author = "Tetsuya Adachi and Kazunobu Ishikawa and Wataru Hida and Hayato Matsumoto and Takayuki Masuda and Fumiko Date and Kazuhiro Ogawa and Kazuhisa Takeda and Kazumichi Furuyama and Yongzhao Zhang and Tomomi Kitamuro and Hiromasa Ogawa and Yukio Maruyama and Shigeki Shibahara",

note = "Funding Information: We thank Dr. Poss K.D. for providing HO-2 −/− mice and Dr. Lusis A.J. for helping backcross these mice. This work was supported in part by Grants-in-Aid for Scientific Research (B) (to S.S.), for Exploratory Research (to S.S.), and for Priority Area (to S.S.) from the Ministry of Education, Science, Sports and Culture of Japan (12670683 and 14570682 to K.I.), and by the 21st Century COE Program Special Research Grant “the Center for Innovative Therapeutic Development for Common Diseases” from the Ministry of Education, Science, Sports and Culture of Japan. This work was also supported in part by the grant to S.S. provided by Uehara Memorial Foundation and grants to K.O. provided by The INAMORI Foundation and The Mochida Memorial Foundation for Medical and Pharmaceutical Research.",

year = "2004",

month = jul,

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doi = "10.1016/j.bbrc.2004.05.195",

language = "English",

volume = "320",

pages = "514--522",

journal = "Biochemical and Biophysical Research Communications",

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T1 - Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2

AU - Adachi, Tetsuya

AU - Ishikawa, Kazunobu

AU - Hida, Wataru

AU - Matsumoto, Hayato

AU - Masuda, Takayuki

AU - Date, Fumiko

AU - Ogawa, Kazuhiro

AU - Takeda, Kazuhisa

AU - Furuyama, Kazumichi

AU - Zhang, Yongzhao

AU - Kitamuro, Tomomi

AU - Ogawa, Hiromasa

AU - Maruyama, Yukio

AU - Shibahara, Shigeki

N1 - Funding Information: We thank Dr. Poss K.D. for providing HO-2 −/− mice and Dr. Lusis A.J. for helping backcross these mice. This work was supported in part by Grants-in-Aid for Scientific Research (B) (to S.S.), for Exploratory Research (to S.S.), and for Priority Area (to S.S.) from the Ministry of Education, Science, Sports and Culture of Japan (12670683 and 14570682 to K.I.), and by the 21st Century COE Program Special Research Grant “the Center for Innovative Therapeutic Development for Common Diseases” from the Ministry of Education, Science, Sports and Culture of Japan. This work was also supported in part by the grant to S.S. provided by Uehara Memorial Foundation and grants to K.O. provided by The INAMORI Foundation and The Mochida Memorial Foundation for Medical and Pharmaceutical Research.

PY - 2004/7/23

Y1 - 2004/7/23

N2 - Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2-/-) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2-/- mice also show attenuated ventilatory responses to hypoxia (10% O2) with normal responses to hypercapnia (10% CO 2), suggesting the impaired oxygen sensing. Importantly, HO-2 -/- mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.

AB - Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2-/-) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2-/- mice also show attenuated ventilatory responses to hypoxia (10% O2) with normal responses to hypercapnia (10% CO 2), suggesting the impaired oxygen sensing. Importantly, HO-2 -/- mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.

KW - Airway chemoreceptor

KW - Carotid body

KW - Heme oxygenase

KW - Hypoxia

KW - Lung

KW - Oxygen

KW - Pulmonary vein

KW - Respiration

KW - Ventilation-perfusion matching

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SN - 0006-291X

VL - 320

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EP - 522

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2

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Keywords

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