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% 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.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Hida
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masuda
authors.forename: Fumiko
authors.initials: F
authors.lastname: Date
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Furuyama
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kitamuro
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ogawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D000818:Animals; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology; D011651:Pulmonary Artery / Q000201:enzymology; D012119:Respiration
chemical_list: D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2