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.
- 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].
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.