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Nitric oxide and zinc contribute to hypoxia induced contractile events in pulmonary endothelial cells
Author(s) -
Bernal Paula Jimena,
Watkins Simon Charles,
Croix Claudette Marie St
Publication year - 2008
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.22.1_supplement.1174.1
Subject(s) - hypoxia (environmental) , chemistry , nitric oxide , hypoxic pulmonary vasoconstriction , zinc , endothelium , vasoconstriction , pulmonary hypertension , endocrinology , lung , medicine , microbiology and biotechnology , constriction , biophysics , biology , oxygen , organic chemistry
We previously reported that acute hypoxia caused a reversible constriction of small non‐muscularized vessels (<100 μM) of the isolated perfused mouse lung (IPL).This led us to study the contractile behavior of isolated endothelial cells using differential interference contrast (DIC) microscopy. We found that rat pulmonary microvascular endothelial cells (RPMVECs) constricted in hypoxia whereas systemic endothelial cells did not. We previously showed that: 1) hypoxia caused NOdependent increases in labile zinc in the IPL that were critically dependent upon the metal binding protein, metallothionein (MT); and 2) hypoxic pulmonary vasoconstriction (HPV) was blunted MT −/− mice or wild‐type mice treated with zinc chelators. We therefore examined a role for NO‐induced zinc release in regulating contraction in RPMVECs, using a NO‐sensitive FRET reporter based on MT and the zinc‐sensitive fluorophore, FluoZin‐3. Hypoxia induced changes in energy transfer consistent with unfolding of MT; accompanied by increases in Zn. Our data suggest that zinc signaling contributes to the effects of hypoxia mediated NO biosynthesis and this pathway may contribute to constriction in lung endothelium.