Differential mechanisms involved in effects of genistein and 17-β-estradiol on porcine coronary arteries

The purpose of this work was to examine the differential mechanisms involved in relaxation induced by genistein and 17-β-estradiol in isolated porcine coronary arteries. Similar to 17-β-estradiol, genistein could dose-dependently relax 30 mM KCl-precontracted coronary artery rings. The pD2 values of genistein and 17-β-estradiol were 4.91 ± 0.13 and 4.98 ± 0.12 respectively. Incubation with N-L-nitro-arginine (L-NNA), endothelium removal or in the presence of a potent inhibitor of protein tyrosine phosphatase sodium orthovanadate did not affect the relaxation induced by genistein, but could partially reduce the vasorelaxation induced by 17-β-estradiol. The relaxations induced by genistein and 17-β-estradiol were unaffected by the estrogen receptor antagonist tamoxifen, the inhibitor of prostanoid synthesis indomethacin and the protein synthesis inhibitor, cycloheximide. In addition, both of genistein and 17-β-estradiol could decrease the contractile responses of KCl, 5-HT and CaCl2, and shift their cumulative concentration-response curves rightward in a parallel manner. These findings suggest that the relaxant effects induced by genistein and 17-β-estradiol are probably mainly due to inhibition of Ca2+ influx through voltage-dependent calcium channels (VDCCs), and are not related to sex hormone receptor and classical genomic activities. Also there is an interesting finding that the relaxing response of 17-β-estradiol is partially endothelium-dependent, but that of genistein is not.