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

  • Pharmacodynamics
  • Published:
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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 μM) 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 μM) 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 μM) significantly induced the generation of intracellular reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB. Pretreatment with AT1 receptor blocker (ARB) losartan (1, 3, 10 μM) 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-κB 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-κB pathway.

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Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (30600817) and the Doctor’s Creative Study of Central South University.

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Authors and Affiliations

  1. Department of Geriatric Medicine, Xiang-Ya Hospital, Central South University, Xiang-Ya Road #141, Changsha, Hunan, 410008, People’s Republic of China

    Mei-Fang Chen, Tian-Lun Yang & Xiu-Mei Xie

  2. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Mei-Fang Chen & Yuan-Jian Li

  3. Clinical Laboratory, First Hospital of Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China

    Bin Lou

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  1. Mei-Fang Chen
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Correspondence to Xiu-Mei Xie.

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Chen, MF., Li, YJ., Yang, TL. et al. Losartan inhibits monocytic adhesion induced by ADMA via downregulation of chemokine receptors in monocytes. Eur J Clin Pharmacol 65, 457–464 (2009). https://doi.org/10.1007/s00228-008-0607-2

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  • DOI: https://doi.org/10.1007/s00228-008-0607-2

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