798 991

Cited 205 times in

Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats

DC Field Value Language
dc.contributor.author오영준-
dc.date.accessioned2015-04-24T17:41:03Z-
dc.date.available2015-04-24T17:41:03Z-
dc.date.issued2009-
dc.identifier.issn0021-8987-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/105869-
dc.description.abstractThere is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate that arginase upregulation leads to endothelial nitric oxide synthase (eNOS) uncoupling and that in vivo chronic inhibition of arginase restores nitroso-redox balance, improves endothelial function, and increases vascular compliance in old rats. Arginase activity in old rats was significantly increased compared with that shown in young rats. Old rats had significantly lower nitric oxide (NO) and higher superoxide (O2(-)) production than young. Acute inhibition of both NOS, with N(G)-nitro-l-arginine methyl ester, and arginase, with 2S-amino- 6-boronohexanoic acid (ABH), significantly reduced O2(-) production in old rats but not in young. In addition, the ratio of eNOS dimer to monomer in old rats was significantly decreased compared with that shown in young rats. These results suggest that eNOS was uncoupled in old rats. Although the expression of arginase 1 and eNOS was similar in young and old rats, inducible NOS (iNOS) was significantly upregulated. Furthermore, S-nitrosylation of arginase 1 was significantly elevated in old rats. These findings support our previously published finding that iNOS nitrosylates and activates arginase 1 (Santhanam et al., Circ Res 101: 692-702, 2007). Chronic arginase inhibition in old rats preserved eNOS dimer-to-monomer ratio and significantly reduced O2(-) production and enhanced endothelial-dependent vasorelaxation to ACh. In addition, ABH significantly reduced vascular stiffness in old rats. These data indicate that iNOS-dependent S-nitrosylation of arginase 1 and the increase in arginase activity lead to eNOS uncoupling, contributing to the nitroso-redox imbalance, endothelial dysfunction, and vascular stiffness observed in vascular aging. We suggest that arginase is a viable target for therapy in age-dependent vascular stiffness.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1249~1257-
dc.relation.isPartOfJOURNAL OF APPLIED PHYSIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAcetylcholine/pharmacology-
dc.subject.MESHAge Factors-
dc.subject.MESHAging*-
dc.subject.MESHAminocaproates/pharmacology*-
dc.subject.MESHAnimals-
dc.subject.MESHAorta/drug effects-
dc.subject.MESHAorta/enzymology-
dc.subject.MESHAorta/physiopathology-
dc.subject.MESHArginase/antagonists & inhibitors*-
dc.subject.MESHArginase/metabolism-
dc.subject.MESHBoron Compounds/pharmacology*-
dc.subject.MESHCarotid Arteries/drug effects-
dc.subject.MESHCarotid Arteries/enzymology-
dc.subject.MESHCarotid Arteries/physiopathology-
dc.subject.MESHCompliance-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHEndothelium, Vascular/drug effects*-
dc.subject.MESHEndothelium, Vascular/enzymology-
dc.subject.MESHEndothelium, Vascular/physiopathology-
dc.subject.MESHEnzyme Inhibitors/pharmacology*-
dc.subject.MESHMale-
dc.subject.MESHNG-Nitroarginine Methyl Ester/pharmacology-
dc.subject.MESHNitric Oxide/metabolism-
dc.subject.MESHNitric Oxide Synthase Type II/antagonists & inhibitors-
dc.subject.MESHNitric Oxide Synthase Type II/metabolism*-
dc.subject.MESHNitric Oxide Synthase Type III/antagonists & inhibitors-
dc.subject.MESHNitric Oxide Synthase Type III/metabolism*-
dc.subject.MESHOxidation-Reduction-
dc.subject.MESHProtein Multimerization-
dc.subject.MESHRats-
dc.subject.MESHRats, Inbred F344-
dc.subject.MESHSuperoxides/metabolism-
dc.subject.MESHTime Factors-
dc.subject.MESHVasodilation/drug effects*-
dc.subject.MESHVasodilator Agents/pharmacology-
dc.titleArginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Anesthesiology (마취통증의학)-
dc.contributor.googleauthorJae Hyung Kim-
dc.contributor.googleauthorLukasz J. Bugaj-
dc.contributor.googleauthorYoung Jun Oh-
dc.contributor.googleauthorTrinity J. Bivalacqua-
dc.contributor.googleauthorSungwoo Ryoo-
dc.contributor.googleauthorKevin G. Soucy-
dc.contributor.googleauthorLakshmi Santhanam-
dc.contributor.googleauthorAlanah Webb-
dc.contributor.googleauthorAndre Camara-
dc.contributor.googleauthorGautam Sikka-
dc.contributor.googleauthorDaniel Nyhan-
dc.contributor.googleauthorArtin A. Shoukas-
dc.contributor.googleauthorMonica Ilies-
dc.contributor.googleauthorDavid W. Christianson-
dc.contributor.googleauthorHunter C. Champion-
dc.contributor.googleauthorDan E. Berkowitz-
dc.identifier.doi10.1152/japplphysiol.91393.2008-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02389-
dc.relation.journalcodeJ01244-
dc.identifier.pmid19661445-
dc.subject.keywordaging-
dc.subject.keywordnitric oxide-
dc.subject.keywordS-nitrosylation-
dc.subject.keywordNOS uncoupling-
dc.contributor.alternativeNameOh, Young Jun-
dc.contributor.affiliatedAuthorOh, Young Jun-
dc.citation.volume107-
dc.citation.number4-
dc.citation.startPage1249-
dc.citation.endPage1257-
dc.identifier.bibliographicCitationJOURNAL OF APPLIED PHYSIOLOGY , Vol.107(4) : 1249-1257, 2009-
dc.identifier.rimsid49899-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.