title: Positive inotropic effects of epigallocatechin-3-gallate (EGCG) involve activation of Na+/H+ and Na+/Ca2+ exchangers.
abstract: BACKGROUND
  There is evidence that the tea catechin epigallocatechin-3-gallate (EGCG) modulates myocardial contractility. However, the underlying mechanisms remain to be determined.
  
  
  OBJECTIVE
  To study potential signalling pathways involved in EGCG-induced contractile parameters.
  
  
  RESULTS
  EGCG increased fractional shortening in rat cardiac myocytes and enhanced intracellular systolic Ca2+ concentrations. In isolated rat hearts, perfusion with EGCG resulted in significant, dose-dependent increase in peak systolic left ventricular pressure, as well as in contraction and relaxation velocities. Heart rate did not change. Inhibition of the beta1-receptor with metoprolol had no influence on the contractile effects of EGCG. Furthermore, levels of cAMP and phosphorylation of phospholamban did not change with EGCG, indicating that the beta-receptor pathway is not involved. The L-type Ca2+ channel inhibitors, nifedipine and gallopamil, failed to modulate EGCG-induced increase in contractility. However, the myocardial effects and intracellular calcium transients stimulated by EGCG were significantly reduced by the antagonist of the Na+/H+ exchanger (NHE) methyl-N-isobutyl amiloride (MIA), and by blocking of the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R7943.
  
  
  CONCLUSIONS
  These results indicate that Ca2+-dependent positive inotropic and lusitropic effects of EGCG are mediated in part via activation of the Na+/H+ exchanger and the reverse mode of the Na+/Ca2+ exchanger in the rat myocardium.
authors.affiliation: Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Lorenz
authors.forename: Niels
authors.initials: N
authors.lastname: Hellige
authors.forename: Philipp
authors.initials: P
authors.lastname: Rieder
authors.forename: Hans-Tilmann
authors.initials: HT
authors.lastname: Kinkel
authors.forename: Christiane
authors.initials: C
authors.lastname: Trimpert
authors.forename: Alexander
authors.initials: A
authors.lastname: Staudt
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.forename: Gert
authors.initials: G
authors.lastname: Baumann
authors.forename: Karl
authors.initials: K
authors.lastname: Stangl
authors.forename: Verena
authors.initials: V
authors.lastname: Stangl
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000187:drug effects* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D002392:Catechin; C045651:epigallocatechin gallate