OBJECTIVES: The soy-isoflavone, genistein, appears to be cardioprotective partly through direct actions on the heart, although the relative benefits between men and women are not fully known. The purpose of the present study was to determine whether gender influences the acute electrophysiological actions of genistein at the level of isolated cardiac myocytes and to elucidate the mechanisms involved. METHODS: Left ventricular myocytes, isolated from weight-matched male and female guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion chamber (37 degrees C). The effects of acute application of genistein on cell shortening and the Ca(2+) transients were measured. Electrophysiological recordings were performed using single electrode voltage-clamp. RESULTS: Genistein increased cell contraction and the Ca(2+) transients in a concentration-dependent manner in myocytes from male guinea-pigs [by 54+/-11% and 22+/-4%, respectively (mean+/-S.E.M., p<0.001, n=18) at 40 microM], while having no significant corresponding effect in those from females. In contrast, genistein increased both parameters in myocytes obtained from male and female rats. The changes in guinea-pigs occurred despite inhibition of the L-type Ca(2+) current in both sexes (n>23, p<0.001). In order to explain these observations, we measured sarcoplasmic reticulum (SR) Ca(2+) contents by integrating the Na(+)/Ca(2+) exchanger currents (I(NCX)) following rapid caffeine application. Genistein increased I(NCX) integrals by 27% in males (n=12, p<0.01) and 20% in females (n=14, p<0.01). The increased SR Ca(2+) load in males, but not females, could be related to an impaired ability of the Na(+)/Ca(2+) exchanger to extrude Ca(2+). CONCLUSIONS: We have demonstrated novel, gender-related differences in the acute cardiac actions of genistein, which can be attributed to actions at distinct points of the intracellular Ca(2+) cycle. Our results suggest that genistein may afford greater cardioprotection in females than in males.
OBJECTIVES: The soy-isoflavone, genistein, appears to be cardioprotective partly through direct actions on the heart, although the relative benefits between men and women are not fully known. The purpose of the present study was to determine whether gender influences the acute electrophysiological actions of genistein at the level of isolated cardiac myocytes and to elucidate the mechanisms involved. METHODS: Left ventricular myocytes, isolated from weight-matched male and female guinea-pigs and rats, were field stimulated at a rate of 1 Hz in a superfusion chamber (37 degrees C). The effects of acute application of genistein on cell shortening and the Ca(2+) transients were measured. Electrophysiological recordings were performed using single electrode voltage-clamp. RESULTS:Genistein increased cell contraction and the Ca(2+) transients in a concentration-dependent manner in myocytes from male guinea-pigs [by 54+/-11% and 22+/-4%, respectively (mean+/-S.E.M., p<0.001, n=18) at 40 microM], while having no significant corresponding effect in those from females. In contrast, genistein increased both parameters in myocytes obtained from male and female rats. The changes in guinea-pigs occurred despite inhibition of the L-type Ca(2+) current in both sexes (n>23, p<0.001). In order to explain these observations, we measured sarcoplasmic reticulum (SR) Ca(2+) contents by integrating the Na(+)/Ca(2+) exchanger currents (I(NCX)) following rapid caffeine application. Genistein increased I(NCX) integrals by 27% in males (n=12, p<0.01) and 20% in females (n=14, p<0.01). The increased SR Ca(2+) load in males, but not females, could be related to an impaired ability of the Na(+)/Ca(2+) exchanger to extrude Ca(2+). CONCLUSIONS: We have demonstrated novel, gender-related differences in the acute cardiac actions of genistein, which can be attributed to actions at distinct points of the intracellular Ca(2+) cycle. Our results suggest that genistein may afford greater cardioprotection in females than in males.