title: Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice.
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.
authors.affiliation: Department of Biology College of Natural Sciences Kangwon National University Chuncheon 200-701, Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Shin
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Ryoo
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D004790:Enzyme Induction; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C544448:Arg1 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase