Evidence that nitric oxide inhibits vascular inflammation and superoxide production via a p47phox-dependent mechanism in mice

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Abstract

Summary 1. Regulation of vascular Nox2-containing NADPH oxidase by p47(phox) plays a pivotal role in atherosclerotic lesion development through superoxide generation. Reduced vascular NO bioavailability is a major contributing factor in the initiation of atherosclerosis as it leads to an increase in adhesion molecule expression for inflammatory cell recruitment into the vessel wall. 2. The aim of this study was to examine whether the anti-oxidant and anti-inflammatory effects of endogenous NO involve inhibition of NADPH oxidase- dependent superoxide production. 3. To inhibit endogenous NO production, male C57Bl/6 wild-type (WT) mice or age-matched p47(phox-/-) mice were treated with L-NAME (100 mg/kg/day for 4 weeks). Weekly blood pressure measurements were taken via tail cuffing. Basal and phorbol dibutyrate (PDB)-stimulated aortic superoxide production was detected using lucigenin- and L-012-enhanced chemiluminescence, respectively. Aortic Nox2, p47(phox) and VCAM-1 expression were measured via Western blotting. Plasma Ang II levels were determined using radioimmunoassay. 4. L-NAME-treated WT mice had significantly higher systolic blood pressure (n=6, P
Original languageEnglish
Pages (from-to)429 - 434
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume37
Issue number4
DOIs
Publication statusPublished - 2010

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