Open Access

Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway

  • Authors:
    • Xu‑Qing Wang
    • Yu‑Ping Zhang
    • Li‑Min Zhang
    • Niu‑Niu Feng
    • Ming‑Zhu Zhang
    • Zi‑Gang Zhao
    • Chun‑Yu Niu
  • View Affiliations

  • Published online on: May 22, 2017     https://doi.org/10.3892/etm.2017.4486
  • Pages: 308-316
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to identify whether sepsis‑induced vascular hyporeactivity is associated with microcirculation disturbance and multiple organ injuries. The current study assessed the impact of resveratrol (Res) treatment on lipopolysaccharide (LPS) challenge mediated vascular hyporeactivity. Effects of Res treatment (30 mg/kg; i.m.) at 1 h following LPS stimulation (5 mg/kg; i.v.) on the survival time, mean arterial pressure (MAP), and maximal difference of MAP (ΔMAP) to norepinephrine (NE; 4.2 µg/kg) in mice were observed. The reactivity to gradient NE of isolated mesenteric arterioles and the association with the RhoA‑RhoA kinase (ROCK)‑myosin light chain phosphatase (MLCP) pathway were investigated by myography, and the signaling molecule protein levels were assessed using ELISA. Res treatment prolonged the survival time of mice subjected to LPS challenge, but did not prevent the LPS‑induced hypotension and increase in ΔMAP. Res treatment and RhoA agonist U‑46619 incubation prevented LPS‑induced vascular hyporeactivity ex vivo, which were suppressed by incubation with ROCK inhibitor Y‑27632. LPS‑induced vascular hyporeactivity was not affected by the MLCP inhibitor okadaic acid incubation, but was further downregulated by the co‑incubation of OA plus Y‑27632. The inhibiting effect of Y‑27632 on Res treatment was eradicated by incubation with U‑46619. Furthermore, RhoA inhibitor C3 transferase did not significantly inhibit the enhancing role of Res treatment, which was further increased by U‑46619 plus C3 transferase co‑incubation. In addition, Res treatment eradicated the LPS‑induced decreases in p‑RhoA and p‑Mypt1 levels and increases in MLCP levels. The results of the present study indicate that post‑treatment of Res significantly ameliorates LPS‑induced vascular hyporeactivity, which is associated with the activation of the RhoA-ROCK-MLCP pathway.
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July-2017
Volume 14 Issue 1

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

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Spandidos Publications style
Wang XQ, Zhang YP, Zhang LM, Feng NN, Zhang MZ, Zhao ZG and Niu CY: Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway. Exp Ther Med 14: 308-316, 2017
APA
Wang, X., Zhang, Y., Zhang, L., Feng, N., Zhang, M., Zhao, Z., & Niu, C. (2017). Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway. Experimental and Therapeutic Medicine, 14, 308-316. https://doi.org/10.3892/etm.2017.4486
MLA
Wang, X., Zhang, Y., Zhang, L., Feng, N., Zhang, M., Zhao, Z., Niu, C."Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway". Experimental and Therapeutic Medicine 14.1 (2017): 308-316.
Chicago
Wang, X., Zhang, Y., Zhang, L., Feng, N., Zhang, M., Zhao, Z., Niu, C."Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway". Experimental and Therapeutic Medicine 14, no. 1 (2017): 308-316. https://doi.org/10.3892/etm.2017.4486