Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice
Experimental & Molecular Medicine
;
: 594-602, 2012.
Article
in English
| WPRIM
| ID: wpr-14963
ABSTRACT
The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Aorta
/
Arginase
/
Vasoconstriction
/
Aging
/
Endothelium, Vascular
/
Up-Regulation
/
Enzyme Induction
/
Reactive Oxygen Species
/
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
/
RNA, Small Interfering
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2012
Type:
Article
Similar
MEDLINE
...
LILACS
LIS