Effects Of Phytoestrogen Genistein On Electrophysiology Of Cardiomyocytes And Underlying Mechanisms

Phytoestrogens are naturally occurring, plant-based dephenolic compounds that are similar in structure and function to estrodiol. Their affinity to estrogen receptor (ER) may be responsible for their effects in tissues. Major categories of phytoestrogens include isoflavones, lignans and coumestans. Genistein (GST) is classified as one of the isoflavones whose common and significant sources are soybeans. In 1987, Akiyama et al proved that GST was also a specific inhibitor of protein tyrosine kinase (PTK). A large body of evidence indicates that phytoestrogens, including GST, may confer cardiovascular protection. For instance, GST caused concentration-dependent relaxation of rabbit coronary artery rings and rat aorta rings; it could also protect against experimental myocardial ischaemia-reperfusion injury in rats; moreover, accumulating evidence suggests that phytoestrogens could inhibit the development of atherosclerosis. As far as the effects of GST on myocardial electrophysiology are concerned, the results are not consistent and the underlying mechanism remains to be determined. Thus, the present work was undertaken to study the effects of GST on action potential (AP) in different hearttissues with intracellular microelectrode technique, and further analyze the possible mechanisms.1. Electrophysiological effects of phytoestrogen genistein onguinea pig papillary musclesThe cardiac electrophysiological effects of genistein(GST) were examined in guinea pig papillary muscle using intracellular microelectrode technique. The results obtained are as follows. (1) Duration of action Potential (APD) in normal papillary muscles were decreased by GST (10-100 jimol/L) in a concentration-dependent manner. (2) In partially depolarized papillary muscles, 50 u.mol/L GST not only reduced APD , but also decreased the amplitute of action potential, overshoot and maximal velocity of phase 0 depolarization. (3) Pretreatment with Nco-nitro-L-arginine(Z--NNA, 5 mmol/L) failed to affect the above effects of GST (50)umol/L) on papillary muscles. (4) 17(3-estradiol (E2, 5 lamol/L) or GST (10 |imol/L) alone did not affect action potential, while GST combined with E2 at the same doses shortened APD significantly. All these results indicate that the effects of GST on papillary muscles are likely due to a decrease of calcium inflow which is not mediated by NO and that GST can have facilitative or synergetic action with E2.