Higenamine exerts an antispasmodic effect on cold‑induced vasoconstriction by regulating the PI3K/Akt, ROS/α2C‑AR and PTK9 pathways independently of the AMPK/eNOS/NO axis

  • Authors:
    • Jianhua Guan
    • Haoming Lin
    • Meijing Xie
    • Meina Huang
    • Di Zhang
    • Shengsuo Ma
    • Wenyan Bian
    • Qianxing Zhan
    • Guoping Zhao
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  • Published online on: June 10, 2019     https://doi.org/10.3892/etm.2019.7656
  • Pages: 1299-1308
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Abstract

The present study aimed to investigate the antispasmodic effect of higenamine on cold‑induced cutaneous vasoconstriction and the underlying molecular mechanisms. A cold‑induced cutaneous vasoconstriction rat model was established and different doses of higenamine were delivered by intravenous injection. The changes of cutaneous regional blood flow (RBF) between groups were analyzed. In vitro, the proliferation of human dermal microvascular endothelial cells was measured by MTT. The NO concentration was detected by a nitrate reductase assay. Flow cytometry was applied to measure reactive oxygen species (ROS) levels. The protein expression levels were detected by western blotting. The results demonstrated that in the model group, RBF declined compared with the normal control group, but was reversed by treatment with higenamine. The expression of endothelial nitric oxide synthase (eNOS), phosphorylated (p)‑eNOS, protein kinase B (Akt1), p‑Akt1, AMP‑activated protein kinase (AMPK) α1 and p‑AMPKα1 was upregulated by hypothermic treatment but was reversed by higenamine treatment. Treatment with higenamine significantly reduced the level of intracellular α2C‑adrenoreceptor (AR) compared with the hypothermia group (P<0.05). Furthermore, the expression of twinfilin‑1 (PTK9) was downregulated in the higenamine and positive control groups compared with the hypothermia group (P<0.05). Compared with the hypothermia group, the levels of ROS and α2C‑AR (intracellular & membrane) were decreased in higenamine and the positive control group (P<0.05 and P<0.01, respectively). This study, to the best of our knowledge, is the first to assess the effects of higenamine on cold‑induced vasoconstriction in vivo and its molecular mechanisms on the PI3K/Akt, AMPK/eNOS/nitric oxide, ROS/α2C‑AR and PTK9 signaling pathways under hypothermia conditions. Higenamine may be a good therapeutic option for Raynaud's phenomenon (RP) and cold‑induced vasoconstriction.
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August-2019
Volume 18 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Guan J, Lin H, Xie M, Huang M, Zhang D, Ma S, Bian W, Zhan Q and Zhao G: Higenamine exerts an antispasmodic effect on cold‑induced vasoconstriction by regulating the PI3K/Akt, ROS/α2C‑AR and PTK9 pathways independently of the AMPK/eNOS/NO axis. Exp Ther Med 18: 1299-1308, 2019
APA
Guan, J., Lin, H., Xie, M., Huang, M., Zhang, D., Ma, S. ... Zhao, G. (2019). Higenamine exerts an antispasmodic effect on cold‑induced vasoconstriction by regulating the PI3K/Akt, ROS/α2C‑AR and PTK9 pathways independently of the AMPK/eNOS/NO axis. Experimental and Therapeutic Medicine, 18, 1299-1308. https://doi.org/10.3892/etm.2019.7656
MLA
Guan, J., Lin, H., Xie, M., Huang, M., Zhang, D., Ma, S., Bian, W., Zhan, Q., Zhao, G."Higenamine exerts an antispasmodic effect on cold‑induced vasoconstriction by regulating the PI3K/Akt, ROS/α2C‑AR and PTK9 pathways independently of the AMPK/eNOS/NO axis". Experimental and Therapeutic Medicine 18.2 (2019): 1299-1308.
Chicago
Guan, J., Lin, H., Xie, M., Huang, M., Zhang, D., Ma, S., Bian, W., Zhan, Q., Zhao, G."Higenamine exerts an antispasmodic effect on cold‑induced vasoconstriction by regulating the PI3K/Akt, ROS/α2C‑AR and PTK9 pathways independently of the AMPK/eNOS/NO axis". Experimental and Therapeutic Medicine 18, no. 2 (2019): 1299-1308. https://doi.org/10.3892/etm.2019.7656