Ellagic acid reduces L-type Ca2+ current and contractility through modulation of NO-GC-cGMP pathways in rat ventricular myocytes

J Cardiovasc Pharmacol. 2014 Dec;64(6):567-73. doi: 10.1097/FJC.0000000000000153.


There is evidence that phenolic structure may have biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. EA effects were investigated on cardiac Ca currents and contractility in rat ventricular myocytes to elucidate the underlying mechanisms. Freshly isolated ventricular myocytes from rat hearts were used. EA dose-dependently reduced Ca currents (ICaL) with EC50 = 23 nM, whereas it did not affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase by SQ-22536 (10 μM) and probucol (5 μM) had no effect on EA modulation of ICaL. Nitric oxide synthase block by L-NAME (500 μM) and of guanylate cyclase by ODQ (1 μM) abolished EA inhibitory effects on ICaL. Moreover, EA blunted ventricular myocytes' fractional shortening in a concentration-dependent manner. In conclusion, EA affects ionic and mechanical properties of rat ventricular myocytes starting at nanomolar concentrations. EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathways. Thus, EA may be useful in pathophysiological conditions such as hypertension and ischemic heart diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / metabolism
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology*
  • Cyclic GMP / metabolism
  • Dose-Response Relationship, Drug
  • Ellagic Acid / administration & dosage
  • Ellagic Acid / pharmacology*
  • Guanylate Cyclase / metabolism
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Male
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Wistar


  • Calcium Channels, L-Type
  • Cardiotonic Agents
  • Ellagic Acid
  • Nitric Oxide
  • Guanylate Cyclase
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester