Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II.
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.
Chen
Mei-Fang
MF
Department of Cardiovascular Medicine, Xiang-Ya Hospital, Changsha, China.
Xie
Xiu-Mei
XM
Yang
Tian-Lun
TL
Wang
Yong-Jin
YJ
Zhang
Xiao-Hong
XH
Luo
Bai-Lin
BL
Li
Yuan-Jian
YJ
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
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