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  3. 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: [email protected].
PMID: 38582274 DOI: 10.1016/j.ejphar.2024.176543
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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