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TGF β‐1 mediated increase in Nox‐4 expression enhances hypoxic pulmonary vasoconstriction in bovine pulmonary arteries
Author(s) -
Ahmad Mansoor,
Zhao Xiangmin,
Kelly Melissa R.,
Kaminski Pawel M.,
Wolin Michael S.
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.1174.3
Subject(s) - apocynin , superoxide , chemistry , horseradish peroxidase , peroxide , hypoxic pulmonary vasoconstriction , ebselen , nadph oxidase , nox , superoxide dismutase , pharmacology , biochemistry , reactive oxygen species , endocrinology , oxidative stress , vasoconstriction , glutathione peroxidase , enzyme , biology , organic chemistry , combustion
Hypoxic pulmonary vasoconstriction (HPV) in de‐endothelialized bovine pulmonary arteries (BPA) is potentially mediated through lowering of superoxide derived peroxide and removal of its basal relaxing effect. Simultaneous force and peroxide measurements showed decreased peroxide levels preceding HPV. Peroxide scavenging with 0.1mM ebselen increased 25mM KCl force and attenuated HPV. BPA pretreated with copper chelator 10mM diethyldithiocarbamate (DETCA), for inactivating Cu Zn SOD, increased 5μM lucigenin‐detectable superoxide and decreased horseradish peroxidase‐luminol detectable peroxide. DETCA also increased 20mM KCl force and attenuated HPV. 48 hr culture of BPA with 10nM Transforming growth factor β‐1 (TGF β‐1) increased NAD(P)H oxidase‐4 (Nox‐4) expression along with superoxide and peroxide levels. 10μM plumbagin (Nox‐4 inhibitor) reversed the increase in superoxide and peroxide with TGF β‐1, however 100μM apocynin (Nox‐2 inhibitor) did not reverse the increased superoxide level. Also TGF β‐1 decreased 20mM KCl force and increased HPV in BPA. Thus, TGF β‐1 mediated increase in Nox‐4 resulted in higher levels of superoxide derived peroxide in BPA which increased HPV. NIH grants (HL31069/HL66331).