Vasorelaxant effect of 3,5,4'-trihydroxy-trans-stilbene (resveratrol) and its underlying mechanism

Inflammopharmacology. 2020 Aug;28(4):869-875. doi: 10.1007/s10787-019-00682-6. Epub 2020 Jan 10.

Abstract

Resveratrol is found in numerous plant-based foods and beverages and is known to have an impact on the cardiovascular system. The aim of this study was to investigate the vasorelaxant effect of resveratrol and its underlying mechanisms by employing an aortic ring assay model. Resveratrol caused relaxation of aortic rings that had been precontracted with phenylephrine in the presence of endothelium or with potassium chloride in endothelium-intact aortic rings. The vasorelaxant effect was decreased in the absence of an endothelium. The mechanisms underlying the vasorelaxant effect of resveratrol were determined through the addition of antagonists. In the presence of the endothelium, indomethacin (a nonselective cyclooxygenase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor), Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), tetraethylammonium (TEA, nonselective calcium activator potassium channel blocker), 4-aminopyridine (4-AP, voltage-dependent K+ channel blocker), barium chloride (BaCl2, inwardly rectifying K+ channel blocker), glibenclamide (non-specific ATP-sensitive K+ channel blocker) and propranolol (β-adrenergic receptor blocker) led to a significant reduction in the vasorelaxation effect induced by resveratrol. Resveratrol was also found to reduce Ca2+ release from the sarcoplasmic reticulum and block calcium channels. In conclusion, resveratrol targets multiple signalling pathways for exerting its vasorelaxant effects in the rat aortic ring model in both the presence and absence of endothelium.

Keywords: Aortic ring assay; Potassium and Calcium channels; Resveratrol; Stilbenoids; Vasorelaxant activity.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Cyclic GMP / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology*
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism
  • Signal Transduction / drug effects
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Calcium Channels
  • Vasodilator Agents
  • Nitric Oxide
  • Cyclic GMP
  • Resveratrol
  • Calcium
  • NG-Nitroarginine Methyl Ester