Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.
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.
Adachi
Tetsuya
T
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Ishikawa
Kazunobu
K
Hida
Wataru
W
Matsumoto
Hayato
H
Masuda
Takayuki
T
Date
Fumiko
F
Ogawa
Kazuhiro
K
Takeda
Kazuhisa
K
Furuyama
Kazumichi
K
Zhang
Yongzhao
Y
Kitamuro
Tomomi
T
Ogawa
Hiromasa
H
Maruyama
Yukio
Y
Shibahara
Shigeki
S
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
D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2