Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status.
Vitamin C and thiol agents improve vasomotor function. To determine whether these compounds directly affect endothelial function, nitric oxide (NO) synthesis was measured in human aortic endothelial cells treated with ascorbic acid or the thiol modulating agents lipoic acid or L-2-oxothiazolidine-4-carboxylic acid (OTC). A dose-dependent increase in A23187-stimulated NO synthesis and elevated cGMP levels were observed in all cases except for OTC. Cellular GSH levels were not significantly increased, and the GSH/GSSG ratio was not significantly affected by treatment of the cells with lipoic acid, OTC, or ascorbic acid. Thus, vitamin C and lipoic acid potentiate endothelial NO synthesis and bioactivity by mechanisms that appear to be independent of cellular GSH levels and redox environment.
Visioli
Francesco
F
Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA. francesco.visioli@unimi.it
Smith
Anthony
A
Zhang
Weijian
W
Keaney
John F
JF
Hagen
Tory
T
Frei
Balz
B
D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D013844:Thiazoles; D053778:Thiazolidines; D009569:Nitric Oxide; D008063:Thioctic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione; D001205:Ascorbic Acid; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid