1. Academic Validation
  2. Resveratrol attenuates cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in the rat mesenteric artery

Resveratrol attenuates cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in the rat mesenteric artery

  • Eur J Pharmacol. 2024 Jun 5:972:176543. doi: 10.1016/j.ejphar.2024.176543.
Qian Li 1 Hanjing Cao 1 Xinya Xu 2 Yumeng Chen 1 Yufang Zhang 1 Yanni Mi 2 Xingmei Zhu 2 Yongheng Shi 2 Jiping Liu 3 Bin Wang 3 Cang-Bao Xu 4 Chuan Wang 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
  • 2 Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China.
  • 3 Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China; Engineering Research Center of Brain Health Industry of Chinese Medicine, Universities of Shaanxi Province, Xianyang 712046, China.
  • 4 Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an 710021, China.
  • 5 Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Xianyang 712046, China; Engineering Research Center of Brain Health Industry of Chinese Medicine, Universities of Shaanxi Province, Xianyang 712046, China. Electronic address: wangchuan@sntcm.edu.cn.
Abstract

Cyclosporin A, an immunosuppressive agent, is extensively utilized for the prevention of transplant rejection and treat autoimmune disease in the clinic, despite its association with a high risk of hypertension development among patients. Resveratrol is a kind of non-flavonoid phenolic compound that widely exists in many Plants. The aim of the present study was to investigate the mechanism by which resveratrol ameliorates cyclosporin A-induced hypertension. The arterial rings of the mesentery were incubated with cyclosporin A and resveratrol in vitro. Rats were administered cyclosporin A and/or resveratrol for 3 weeks in vivo. Blood pressure was measured via the tail arteries. Vasoconstriction curves were recorded using a sensitive myograph. The protein expression was evaluated through Western blotting. This study demonstrated that resveratrol mitigated the cyclosporin A-induced increase in blood pressure in rats. Furthermore, resveratrol markedly inhibited the cyclosporin A-induced upregulation of thromboxane A2 receptor-mediated vasoconstriction in the rat mesenteric artery both in vitro and in vivo. Moreover, resveratrol activated AMPK/SIRT1 and inhibited the MAPK/NF-κB signaling pathway. In conclusion, resveratrol restored the cyclosporin A-induced upregulation of the thromboxane A2 receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in rats.

Keywords

AMPK/SIRT1; Cyclosporin A; Hypertension; Resveratrol; Thromboxane A(2) receptor.

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