title: Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II.
abstract: Previous investigations have demonstrated that angiotensin (Ang) II induces inflammatory reactions and asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, might be a novel inflammatory factor. Endothelial cell activation was induced by incubation with Ang II or ADMA. Incubation with Ang II (10(-6) M) for 24 h elevated the levels of ADMA and decreased the levels of nitrite/nitrate concomitantly with a significant increase in the expression of protein arginine methyltransferase and a decrease in the activity of dimethylarginine dimethylaminohydrolase (DDAH). Exposure to Ang II (10(-6) M for 24 h) also enhanced intracellular ROS elaboration and the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8, upregulated chemokine receptor CXCR2 mRNA expression, increased adhesion of endothelial cells to monocytes and induced a significant increase in the activity of nuclear factor (NF)-kappaB, which was attenuated by pretreatment with the Ang II receptor blocker losartan (1, 3 and 10 muM). Exogenous ADMA (30 microM) also increased ROS generation and the levels of TNF-alpha and IL-8, decreased the levels of nitrite/nitrate, upregulated CXCR2 gene expression, increased endothelial cell binding with monocytes and activated the NF-kappaB pathway, which was inhibited by pretreatment with losartan or L-arginine. These data suggest that ADMA is a potential proinflammatory factor and may be involved in the inflammatory reaction induced by Ang II.
authors.affiliation: Department of Cardiovascular Medicine, Xiang-Ya Hospital, Changsha, China.
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Chen
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Xie
authors.forename: Tian-Lun
authors.initials: TL
authors.lastname: Yang
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Wang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Luo
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000804:Angiotensin II / Q000633:toxicity*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D019808:Losartan / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D011484:Protein-Arginine N-Methyltransferases / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014471:Umbilical Veins; D014657:Vasculitis / Q000139:chemically induced*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D019808:Losartan