Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities.
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 approximately 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 micromol/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 micromol/L) and specifically with high concentrations of vitamin E (100 micromol/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
Sibel
S
Department of Medicine, Institute of Clinical Science Block B, Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK.
McKeown
Pascal P
PP
Bayraktutan
Ulvi
U
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology; D001205:Ascorbic Acid / Q000494:pharmacology; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*
D000975:Antioxidants; D014815:Vitamins; D013481:Superoxides; D014810:Vitamin E; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; D001205:Ascorbic Acid