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Cytochrome P‐450 2J epoxygenase gene function in murine hypoxic pulmonary vasoconstriction (HPV)
Author(s) -
Beloiartsev Arkadi,
Zhou Guo Ling,
Bloch Kenneth D.,
Seed Brian,
Zapol Warren M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.700.1
Subject(s) - epoxygenase , hypoxic pulmonary vasoconstriction , medicine , lung , hypoxia (environmental) , vasoconstriction , anesthesia , occlusion , pulmonary artery , pulmonary function testing , cytochrome p450 , chemistry , oxygen , organic chemistry , metabolism
Recent studies suggest that cytochrome P‐450 (CYP) epoxygenase‐derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of the pulmonary vascular tone. To assess the role of the CYP2J‐signaling pathway in HPV, we studied CYP2J +/+ and CYP2J −/− mice, as well as CYP2J −/− mice carrying a transgene specifying human CYP2J (CYP2J −/− ‐Tg). Mice were anesthetized, intubated, and ventilated at F I O 2 =1. After thoracotomy, pulmonary artery pressure (PAP) and left lung blood flow (QLPA) were measured before and during transient inferior vena cava occlusion. Left pulmonary vascular resistance (LPVR) was calculated from the slope of the PAP‐QLPA relationship. The pulmonary vasoconstrictor response to unilateral left lung hypoxia was estimated by comparing LPVR before and after left main stem bronchial occlusion (LMBO). LMBO increased LPVR in CYP2J +/+ and CYP2J −/− ‐Tg mice but not in CYP2J −/− mice (see Table). P a O 2 during LMBO was greater in CYP2J +/+ and CYP2J −/− ‐Tg mice than in CYP2J −/− mice. Administration of MS‐PPOH, a selective inhibitor of CYP‐mediated epoxygenation, blocked the ability of LMBO to increase LPVR in CYP2J +/+ mice. Taken together, these results indicate that CYP2J epoxygenase contributes importantly to HPV in mice. (Supported by MGH, Department of Anesthesia, Critical Care and Pain Medicine).