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

Research output: Contribution to journalArticlepeer-review

70 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 languageEnglish
Pages (from-to)514-522
Number of pages9
JournalBiochemical and biophysical research communications
Volume320
Issue number2
DOIs
Publication statusPublished - 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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