Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a key signaling molecule in vascular homeostasis. Loss of NO bioavailability due to reduced synthesis and increased scavenging by reactive oxygen species is a cardinal feature of endothelial dysfunction in vascular disease states. The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of eNOS activity: when BH4 availability is limiting, eNOS no longer produces NO but instead generates superoxide. In vascular disease states, there is oxidative degradation of BH4 by reactive oxygen species. However, augmentation of BH4 concentrations in vascular disease by pharmacological supplementation, by enhancement of its rate of de novo biosynthesis or by measures to reduce its oxidation, has been shown in experimental studies to enhance NO bioavailability. Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease.

Original publication

DOI

10.1161/01.ATV.0000110785.96039.f6

Type

Journal article

Journal

Arterioscler Thromb Vasc Biol

Publication Date

03/2004

Volume

24

Pages

413 - 420

Keywords

Animals, Biological Availability, Biopterin, Coenzymes, Diabetes Mellitus, Enzyme Induction, GTP Cyclohydrolase, Humans, Hypercholesterolemia, Hypertension, Mice, Mice, Mutant Strains, Models, Animal, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Oxidation-Reduction, Oxidative Stress, Pterins, Rabbits, Rats, Rats, Inbred Strains, Superoxides, Vascular Diseases