PMID- 19156404
OWN - NLM
STAT- MEDLINE
DCOM- 20090709
LR  - 20211020
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 65
IP  - 5
DP  - 2009 May
TI  - Losartan inhibits monocytic adhesion induced by ADMA via downregulation of 
      chemokine receptors in monocytes.
PG  - 457-64
LID - 10.1007/s00228-008-0607-2 [doi]
AB  - OBJECTIVE: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide 
      synthase (NOS) inhibitor, can induce the adhesiveness of monocytes to vascular 
      endothelium, and chemokines play an important role in this process. The present 
      study was carried out to test whether the inhibitory effect of losartan on 
      ADMA-induced monocytic adhesion is mediated by chemokine receptors. METHODS: 
      Human monocytoid cells (THP-1) were incubated with exogenous ADMA (30 microM) for 
      4 or 24 h in the absence or presence of losartan. The monocytic adhesion, the 
      levels of chemokines, and the expression of chemokine receptors were determined. 
      The possible signal pathway was also explored. RESULTS: In cultured monocytes, 
      ADMA (30 microM) markedly increased monocytic adhesion to endothelial cells, 
      elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and 
      interleukin-8 (IL-8), and upregulated the mRNA expression of chemokine receptors 
      CCR2 and CXCR2. Exposure to ADMA (30 microM) significantly induced the generation 
      of intracellular reactive oxygen species (ROS) and activation of nuclear factor 
      (NF)-kappaB. Pretreatment with AT1 receptor blocker (ARB) losartan (1, 3, 10 
      microM) attenuated monocytic adhesiveness elicited by ADMA and downregulated the 
      expression of CCR2 and CXCR2 mRNA, accompanied by a significant decrease in ROS 
      generation and NF-kappaB activity and expression. CONCLUSION: The present study 
      suggests that the inhibitory effect of losartan on ADMA-induced monocytic 
      adhesion may be related to downregulation of chemokine receptors by inhibiting 
      the ROS/NF-kappaB pathway.
FAU - Chen, Mei-Fang
AU  - Chen MF
AD  - Department of Geriatric Medicine, Xiang-Ya Hospital, Central South University, 
      Xiang-Ya Road #141, Changsha, Hunan 410008, People's Republic of China.
FAU - Li, Yuan-Jian
AU  - Li YJ
FAU - Yang, Tian-Lun
AU  - Yang TL
FAU - Lou, Bin
AU  - Lou B
FAU - Xie, Xiu-Mei
AU  - Xie XM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090122
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Chemokine)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Cell Adhesion/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/*drug effects
MH  - Endothelial Cells/drug effects
MH  - Humans
MH  - Interleukin-8/biosynthesis
MH  - Losartan/*pharmacology
MH  - Monocytes/*cytology/*drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Time Factors
EDAT- 2009/01/22 09:00
MHDA- 2009/07/10 09:00
CRDT- 2009/01/22 09:00
PHST- 2008/07/26 00:00 [received]
PHST- 2008/12/18 00:00 [accepted]
PHST- 2009/01/22 09:00 [entrez]
PHST- 2009/01/22 09:00 [pubmed]
PHST- 2009/07/10 09:00 [medline]
AID - 10.1007/s00228-008-0607-2 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2009 May;65(5):457-64. doi: 10.1007/s00228-008-0607-2. Epub 
      2009 Jan 22.