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Connexin 40 is essential for hypoxic pulmonary vasoconstriction
Author(s) -
Wang Liming,
Isakson Brant,
Wit Cor,
Kuppe Hermann,
Kuebler Wolfgang M
Publication year - 2009
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.23.1_supplement.1002.7
Subject(s) - hypoxic pulmonary vasoconstriction , connexin , hypoxia (environmental) , vasoconstriction , vasodilation , pulmonary artery , lung , medicine , arteriole , chemistry , gap junction , biology , cardiology , endocrinology , microbiology and biotechnology , circulatory system , oxygen , intracellular , organic chemistry
Hypoxic pulmonary vasoconstriction (HPV) has traditionally been attributed exclusively to O 2 sensing in pulmonary vascular smooth muscle cells (PASMC). Yet, the predominant site of gas exchange, and hence, the ideal site for O 2 sensing is in pulmonary capillaries, where PASMCs are absent. The spatial separation between a capillary O 2 sensor and PASMC in upstream arterioles would require a retrograde propagation of signals along the endothelial layer. Connexin 40 (Cx40) is expressed in lung endothelial cells and mediates conducted responses in the systemic circulation. Here, in isolated mouse lungs, we tested our hypothesis that Cx40 plays a critical role in HPV. HPV was quantified as increase in pulmonary artery pressure (PAP) in response to hypoxic ventilation (1% F i O 2 ). Intrinsic pulmonary vascular resistance (R 0 ) was determined by nonlinear regression analysis of pressure‐flow curves. Hypoxia‐induced increases in PAP and R 0 were attenuated by 75% in lungs perfused with the nonspecific gap junction blocker 18α‐glycyrrhetinic acid, by 55% with Cx40 specific mimetic peptide Gap27 40 , and by 64% in Cx40 −/− mice. The role of Cx40 is specific for HPV, since the vasoconstriction response to angiotensin II remained unaffected in all groups. Our data demonstrate a critical role of Cx40 in HPV, and suggest that microvascular endothelial cells may propagate the hypoxic signal to upstream arterioles via endothelial Cx40.