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

Michał Wiciński,Karol Górski,Bartosz Malinowski,Katarzyna Pawlak-Osińska,Paweł Szychta,Eryk Wódkiewicz,Maciej Słupski,Paweł Rajewski,Maciej Walczak

doi:10.1155/2020/9012071

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.

Highlights

Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. ey are referred to as phytoestrogens—the plant hormones. e natural sources of resveratrol are mulberry, rhubarb, peanuts, and eucalyptus, Scots pine, or Japanese knotweed [1]
DAG stimulates the activity of protein kinase C, which is responsible for the inclusion of Ras superfamily members into the signaling pathway [8]. e interaction between one of their representatives—member A (RhoA) and Rho-kinase (ROK)— results in a decrease of myosin light chain phosphatase (MLCP) activity. us, inhibited phosphatase is unable to dephosphorylate myosin light chain. is process increases the sensitivity of the contractile apparatus of the Vascular smooth muscle cells (VSMCs) to Ca2+, which maintains the constriction [9]. e aim of the present study was to determine the influence of resveratrol application along with the inhibition of certain molecular factors on VMSCs constriction triggered by phenylephrine
Our study using classical pharmacometric methods revealed complex mechanisms of vascular smooth muscle hyporeactivity after four weeks of resveratrol administration. e overall assessment of vasoreactivity in the presence of resveratrol should take into account both the mechanisms associated with the receptor pathways and the extrareceptor components, such as G-protein-coupled enzymes, ion channels, or regulation at the level of endothelial cells

Summary

Introduction

Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. ey are referred to as phytoestrogens—the plant hormones. e natural sources of resveratrol are mulberry, rhubarb, peanuts, and eucalyptus, Scots pine, or Japanese knotweed [1]. E natural sources of resveratrol are mulberry, rhubarb, peanuts, and eucalyptus, Scots pine, or Japanese knotweed [1]. Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. It is believed, that the main source of resveratrol is grapes, in particular, their peel and seeds, in which the resveratrol concentration can be as high as. Following oral administration in humans, approximately 70% of resveratrol is absorbed [3]. Resveratrol and its metabolites have an affinity for numerous cytochrome P450 isoenzymes (CYP450). E first studies describing the beneficial action of resveratrol in the prophylaxis of coronary artery disease appeared at the beginning of the 20th century [4] Resveratrol and its metabolites have an affinity for numerous cytochrome P450 isoenzymes (CYP450). e first studies describing the beneficial action of resveratrol in the prophylaxis of coronary artery disease appeared at the beginning of the 20th century [4].

Methods

Results

Conclusion