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Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities

Ulker, Sible; McKeown, Pascal; Bayraktutan, Ulvi


Sible Ulker

Pascal McKeown


Antioxidant vitamins C and E have protective properties in genetic hypertension associated with enhanced
oxidative stress. This study investigated whether vitamins C and/or E modulate vascular function by regulating
enzymatic activities of endothelial nitric oxide synthase (eNOS) and NAD(P)H oxidase using thoracic aortas of 20- to
22-week-old male spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar-Kyoto
rats (WKY). SHR aortas had impaired relaxant responses to acetylcholine but not to sodium nitroprusside, despite an
2-fold increase in eNOS activity and NO release. The levels of superoxide anion (O2
), a potent NO scavenger, and
NAD(P)H oxidase activity were also 2-fold higher in SHR aortas. Mechanical but not pharmacological inactivation of
endothelium (by rubbing and 100 mol/L L-NAME, respectively) significantly abrogated O2
in both strains.
Treatments of SHR aortas with NAD(P)H oxidase inhibitors, namely diphenyleneiodinium and apocynin, significantly
diminished O2
production. The incubation of SHR aortas with different concentrations of vitamin C (10 to 100 mol/L)
and specifically with high concentrations of vitamin E (100 mol/L) improved endothelial function, reduced superoxide
production as well as NAD(P)H oxidase activity, and increased eNOS activity and NO generation in SHR aortas to the
levels observed in vitamin C- and E-treated WKY aortas. Our results reveal endothelial NAD(P)H oxidase as the major
source of vascular O2
in SHR and also show that vitamins C and E are critical in normalizing genetic endothelial
dysfunction through regulation of eNOS and NAD(P)H oxidase activities.


Ulker, S., McKeown, P., & Bayraktutan, U. (2003). Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities. Hypertension, 41,

Journal Article Type Article
Publication Date Jan 1, 2003
Deposit Date Oct 26, 2006
Publicly Available Date Aug 22, 2008
Journal Hypertension
Print ISSN 2224-1485
Publisher Publishing House Zaslavsky
Peer Reviewed Peer Reviewed
Volume 41
Keywords nitric oxide endothelium enzymes antioxidants hypertension, experimental vitamins
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