© 2008 European Society of Cardiology
Positive inotropic effects of epigallocatechin-3-gallate (EGCG) involve activation of Na+/H+ and Na+/Ca2+ exchangers
a Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité — Universitätsmedizin Berlin Campus Mitte, Germany
b Institut für Diagnostische Radiologie, Universitäts-Spital Zürich Zürich, Switzerland
c Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald Germany
* Corresponding author. Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité — Universitätsmedizin Berlin, CCM, Charitéplatz 1, D-10117 Berlin, Germany. Tel.: +49 30 450 513 153; fax: +49 30 450 513 932. E-mail address: verena.stangl{at}charite.de (V. Stangl).
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Abstract |
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Background: There is evidence that the tea catechin epigallocatechin-3-gallate (EGCG) modulates myocardial contractility. However, the underlying mechanisms remain to be determined.
Aims: To study potential signalling pathways involved in EGCG-induced contractile parameters.
Methods and 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 β1-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.
Conclusion: 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.
Key Words: EGCG • Myocardium • Contractility • Inotropic • Rat
Received September 4, 2007; Revised January 23, 2008; Accepted March 6, 2008