Format

Send to

Choose Destination
See comment in PubMed Commons below
Curr Opin Pharmacol. 2013 Apr;13(2):161-7. doi: 10.1016/j.coph.2013.01.006. Epub 2013 Feb 7.

Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease.

Author information

1
Department of Pharmacology, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany.

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.

PMID:
23395155
DOI:
10.1016/j.coph.2013.01.006
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center