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% CO2), 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.

• Authors: 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
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 320 Issue 2 Pg. 514-22 (Jul 23 2004) ISSN: 0006-291X [Print] United States
• PMID: 15219859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heme Oxygenase (Decyclizing)
• heme oxygenase-2

Topics

• Animals
• Female
• Heme Oxygenase (Decyclizing) (genetics, physiology)
• Humans
• Hypoxia (enzymology, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardium (enzymology)
• Pulmonary Artery (enzymology)
• Respiration