Resveratrol's Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition

Biomed Res Int. 2020 Jan 21:2020:9012071. doi: 10.1155/2020/9012071. eCollection 2020.

Abstract

Resveratrol (3,5,4'-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res-). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Arteries / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Signaling / drug effects
  • Cyclic GMP / antagonists & inhibitors
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Phenylephrine / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Resveratrol / pharmacology*
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Calcium Channel Blockers
  • Protein Kinase Inhibitors
  • Phenylephrine
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • rho-Associated Kinases
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP
  • Resveratrol