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Nitric‐oxide, zinc and hypoxia‐induced contraction of isolated pulmonary endothelium
Author(s) -
St. Croix Claudette Marie,
Leelavanichkul Karanee,
Pitt Bruce R,
Lanni Frederick,
Watkins Simon C
Publication year - 2006
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.20.4.a407
Subject(s) - vasoconstriction , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , nitric oxide , intracellular , endothelium , zinc , chemistry , pulmonary hypertension , lung , vascular smooth muscle , metallothionein , biology , medicine , endocrinology , oxygen , biochemistry , smooth muscle , organic chemistry
Although hypoxic pulmonary vasoconstriction (HPV) has been reported to affect all segments of the pulmonary circulation relatively little is known regarding vasoconstriction of intra‐acinar arterioles. We used laser scanning confocal microscopy of the subpleural vasculature of the isolated perfused (Tie2‐GFP) mouse lung and observed a 10–15% decrease in vessel diameter in pulmonary microvessels (<40 microns) in response to hypoxia. The increase in total pulmonary vascular resistance was sensitive to the zinc chelator, TPEN, and was not apparent in null mice of the major intracellular zinc binding protein, metallothionein, suggesting an important role for (NO mediated) elevations in intracellular zinc in hypoxic vasoconstriction. Using high resolution differential interference contrast imaging of collagen‐embedded cells we showed that low oxygen and zinc cause constriction of isolated cultured pulmonary microvascular endothelial cells from rat (and mouse). The effect is specific in that rat aortic smooth muscle cells relaxed to hypoxia. These data, in combination with that obtained using fluorescent reporter molecules for nitric oxide (NO) and zinc, suggest that hypoxia induced increases in NO biosynthesis result in changes in intracellular zinc in pulmonary endothelium that in turn may contribute to vasoconstriction of pulmonary microvessels.