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

Ulker, Sible and McKeown, Pascal and Bayraktutan, Ulvi (2003) Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities. Hypertension, 41 . pp. 534-539.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: nitric oxide endothelium enzymes antioxidants hypertension, experimental vitamins
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Medicine > Division of Clinical Neuroscience
Related URLs:
URLURL Type
http://hyper.ahajournals.org/Publisher
Depositing User: Sayers, Hazel
Date Deposited: 26 Oct 2006
Last Modified: 16 Aug 2013 07:27
URI: http://eprints.nottingham.ac.uk/id/eprint/426

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