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Modulation of the Contractile Response of Bovine Pulmonary Arteries to Hypoxia by Plumbagin, an inhibitor of Nox oxidase‐4
Author(s) -
Ahmad Mansoor,
Kaminski Pawel M.,
Wolin Michael S.
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.21.6.a922-b
Bovine pulmonary arteries (BPA) contain the Nox‐2 and Nox‐4 forms of NADPH oxidases. BPA contract to hypoxia through a mechanism potentially involving lowering hydrogen peroxide originating from Nox oxidase‐derived superoxide. Inhibition of Nox‐2 activation with 0.1mM apocynin or 50μM gp91ds‐tat lowers superoxide (detected by 5μM lucigenin chemiluminescence) without preventing contraction to hypoxia. Treatment of BPA with 10μM plumbagin, a potential inhibitor of Nox‐4, increased force in the presence of 21% oxygen and eliminated further contraction caused by hypoxia. Plumbagin lowered superoxide further in the presence of the Nox‐2 inhibitors gp91ds‐tat and apocynin. Mitochondrial probes (10μM rotenone, antimycin) decreased superoxide levels in BPA but did not affect contraction to hypoxia. The actions of plumbagin are consistent with hypoxia removing a peroxide‐mediated relaxation originating from superoxide produced by Nox‐4. Support by NIH grants HL31069, HL43023 and HL66331.