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.

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.

• Authors: Qian Li, Hanjing Cao, Xinya Xu, Yumeng Chen, Yufang Zhang, Yanni Mi, Xingmei Zhu, Yongheng Shi, Jiping Liu, Bin Wang, Cang-Bao Xu, Chuan Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 972 Pg. 176543 (Jun 05 2024) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 38582274 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier B.V. All rights reserved.

Chemical References

• Resveratrol
• Cyclosporine
• Sirtuin 1
• NF-kappa B
• AMP-Activated Protein Kinases
• Sirt1 protein, rat
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Resveratrol (pharmacology)
• Cyclosporine (pharmacology)
• Sirtuin 1 (metabolism)
• Mesenteric Arteries (drug effects, metabolism)
• Hypertension (drug therapy, metabolism, physiopathology)
• Male
• NF-kappa B (metabolism)
• Up-Regulation (drug effects)
• Rats
• AMP-Activated Protein Kinases (metabolism)
• Rats, Sprague-Dawley
• Vasoconstriction (drug effects)
• Blood Pressure (drug effects)
• Signal Transduction (drug effects)
• Mitogen-Activated Protein Kinases (metabolism)