Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease.

Abstract

Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) is an antihypertensive, antithrombotic and anti-atherosclerotic molecule. Hypercholesterolemia leads to a reduction in vascular NO bioavailability. This is attributed to a dysfunction of the eNOS enzyme and a reduced eNOS activity. NADPH oxidase-mediated oxidative stress leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide-producing enzyme. As a consequence of eNOS uncoupling, NO production is reduced and the pre-existing oxidative stress is enhanced, which contribute significantly to atherogenesis. Therefore, pharmacological approaches that prevent eNOS uncoupling and enhance eNOS activity are of therapeutic interest. Angiotensin-converting enzyme inhibitors, AT1 receptor blockers, statins, nebivolol and resveratrol have been shown to reverse eNOS uncoupling and to stimulate eNOS activity concurrently. Molecular mechanisms of the aforementioned drugs/compounds on eNOS functionality is summarized and discussed in this review.

• Authors: Huige Li, Ulrich Förstermann
• Journal: Current opinion in pharmacology (Curr Opin Pharmacol) Vol. 13 Issue 2 Pg. 161-7 (Apr 2013) ISSN: 1471-4973 [Electronic] England
• PMID: 23395155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013. Published by Elsevier Ltd.

Chemical References

• Nitric Oxide
• Nitric Oxide Synthase Type III

Topics

• Animals
• Humans
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Vascular Diseases (drug therapy, metabolism)