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. Epub 2024 Apr 4.

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.

MeSH terms

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

Substances

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