Vascular effects following homozygous disruption of p47(phox) : An essential component of NADPH oxidase.
BACKGROUND
Evidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase. We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure.


RESULTS
An examination of aortic rings from wild-type mice and mice with homozygous targeted disruptions in p47(phox) revealed that p47(phox) knockout mice had a reduction in vascular superoxide production. However, analyses of apoE -/- p47(phox)+/+ and apoE -/- p47(phox) -/- strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47(phox) knockout mice revealed no differences in either basal blood pressure or the rise in blood pressure seen after the pharmacological inhibition of nitric oxide synthase.


CONCLUSIONS
NADPH oxidase contributes to basal vascular superoxide production. However, the absence of a functional oxidase does not significantly affect the progression of atherosclerosis in the standard mouse apoE -/- model, nor does it significantly influence basal blood pressure.
Hsich
E
E
Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute, and the Laboratory of Host Defenses, National Institute of Health, Bethesda, MD 20892, USA.
Segal
B H
BH
Pagano
P J
PJ
Rey
F E
FE
Paigen
B
B
Deleonardis
J
J
Hoyt
R F
RF
Holland
S M
SM
Finkel
T
T
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006720:Homozygote; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D019331:NG-Nitroarginine Methyl Ester