Positive inotropic effects of epigallocatechin-3-gallate (EGCG) involve activation of Na+/H+ and Na+/Ca2+ exchangers.
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.
Lorenz
Mario
M
Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Germany.
Hellige
Niels
N
Rieder
Philipp
P
Kinkel
Hans-Tilmann
HT
Trimpert
Christiane
C
Staudt
Alexander
A
Felix
Stephan B
SB
Baumann
Gert
G
Stangl
Karl
K
Stangl
Verena
V
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
D002316:Cardiotonic Agents; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D002392:Catechin; C045651:epigallocatechin gallate