Skip to main content

Resveratrol reduces myofibroblast arrhythmogenicity


Among grape skin polyphenols, trans-resveratrol (RES) has been reported to slow the development of cardiac fibrosis and to affect myofibroblast (MFB) differentiation. Because MFBs induce slow conduction and ectopic activity following heterocellular gap junctional coupling to cardiomyocytes, we investigated whether RES and its main metabolites affect arrhythmogenic cardiomyocyte-MFB interactions.


Experiments were performed with patterned growth strands of neonatal rat ventricular cardiomyocytes coated with cardiac MFBs. Impulse propagation characteristics were measured optically using voltage-sensitive dyes. Long-term video recordings served to characterize drug-related effects on ectopic activity. Data are given as means ± S.D. (n = 4–20).


Exposure of pure cardiomyocyte strands to RES at concentrations up to 10 µmol/L had no significant effects on impulse conduction velocity (θ) and maximal action potential upstroke velocities (dV/dtmax). By contrast, in MFB-coated strands exhibiting slow conduction, RES enhanced θ with an EC50 of ~10 nmol/L from 226 ± 38 to 344 ± 24 mm/s and dV/dtmax from 48 ± 7 to 69 ± 2%APA/ms, i.e., to values of pure cardiomyocyte strands (347 ± 33 mm/s; 75 ± 4%APA/ms). Moreover, RES led to a reduction of ectopic activity over the course of several hours in heterocellular preparations. RES is metabolized quickly in the body; therefore, we tested the main known metabolites for functional effects and found them similarly effective in normalizing conduction with EC50s of ~10 nmol/L (3-OH-RES), ~20 nmol/L (RES-3-O-β-glucuronide) and ~10 nmol/L (RES-sulfate), respectively. At these concentrations, neither RES nor its metabolites had any effects on MFB morphology and α-smooth muscle actin expression. This suggests that the antiarrhythmic effects observed were based on mechanisms different from a change in MFB phenotype.


The results demonstrate that RES counteracts MFB-dependent arrhythmogenic slow conduction and ectopic activity at physiologically relevant concentrations. Because RES is rapidly metabolized following intestinal absorption, the finding of equal antiarrhythmic effectiveness of the main RES metabolites warrants their inclusion in future studies of potentially beneficial effects of these substances on the heart.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Christian Rosker.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Rosker, C., Salvarani, N. & Rohr, S. Resveratrol reduces myofibroblast arrhythmogenicity. BMC Pharmacol 10 (Suppl 1), A3 (2010).

Download citation

  • Published:

  • DOI:


  • Resveratrol
  • Grape Skin
  • Ventricular Cardiomyocytes
  • Slow Conduction
  • Ectopic Activity