Losartan inhibits monocytic adhesion induced by ADMA via downregulation of chemokine receptors in monocytes.

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  • Author(s): Chen MF;Chen MF; Li YJ; Yang TL; Lou B; Xie XM
  • Source:
    European journal of clinical pharmacology [Eur J Clin Pharmacol] 2009 May; Vol. 65 (5), pp. 457-64. Date of Electronic Publication: 2009 Jan 22.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: Germany NLM ID: 1256165 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1041 (Electronic) Linking ISSN: 00316970 NLM ISO Abbreviation: Eur J Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin, New York, Springer.
    • Subject Terms:
      Down-Regulation/*drug effects ; Losartan/*pharmacology ; Monocytes/*cytology ; Monocytes/*drug effects ; Receptors, Chemokine/*metabolism; Arginine/analogs & derivatives ; Arginine/pharmacology ; Cell Adhesion/drug effects ; Cells, Cultured ; Chemokine CCL2/biosynthesis ; Dose-Response Relationship, Drug ; Endothelial Cells/drug effects ; Humans ; Interleukin-8/biosynthesis ; Monocytes/metabolism ; NF-kappa B/metabolism ; RNA, Messenger/biosynthesis ; Receptors, Chemokine/genetics ; Time Factors
    • Abstract:
      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.
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    • Accession Number:
      0 (Chemokine CCL2)
      0 (Interleukin-8)
      0 (NF-kappa B)
      0 (RNA, Messenger)
      0 (Receptors, Chemokine)
      63CV1GEK3Y (N,N-dimethylarginine)
      94ZLA3W45F (Arginine)
      JMS50MPO89 (Losartan)
    • Publication Date:
      Date Created: 20090122 Date Completed: 20090709 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00228-008-0607-2
    • Accession Number:
      19156404