Effects Of Genistein On Cardiovascular System And Its Mechanism

Phytoestrogens are naturally occurring, derived from soybeans dephenolic compounds that are similar in structure and function to estrodiol, and bind to estrogen receptors and have estrogen-like cardiovascular effects. Major categories of phytoestrogens include isoflavones, lignans and coumestans. Genistein (GST) is classified as one of the isoflavones. A large body of evidence indicates that phytoestrogens, including GST, may confer cardiovascular protection. For instance, GST could play a role in preventing arteriosclerosis, inhibiting proliferation of vascular smooth cells and angiogenesis, relaxing arteries, thus, it had protective action on cardiovascular system. Our previous studies demonstrated that GST reduced duration of action potential (APD) in normal papillary muscles. In partially depolarized papillary muscles, GST not only reduced APD, but also decreased the amplitude of action potential (APA), overshoot (OS) and maximal velocity of phase 0 depolarization (Vmax); Pretreatment with GST markedly inhibited delayed afterdepolarization (DAD) and triggered activity (TA) induced by ouabain in a concentration-dependent manner. GST reduced maximal rate of depolarization, the velocity of diastolic (phase 4) depolarization (VDD), rate of spontaneous firing (RSF), and the amplitude of action potential in a concentration-dependent manner in sinoatrial node and atrioventricular node pacemaker cells of rabbits. GST also decreased the velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) in human artrial fibers. However, little is known about other cardiovascular actions of GST. The purposes of the present study were to observe: (1) Action of genistein on tension of isolated femoral artery and its mechanism in rabbits; (2) Responses of regional vascular beds to local injection of genistein in rats; (3) Effects of phytoestrogen genistein on myocardial ischemia/reperfusion injury and apoptosis in rabbits; (4) Effects of genistein on intracellular free calcium concentration in guinea pig ventricular myocytes; (5) Effect of genistein on L-type calcium current in guinea pig ventricular myocytes.1 Action of genistein on tension of isolated femoral artery and its mechanism in rabbits The phytoestrogen genistein has been shown to relax preconstricted arteries in vitro; the mechanism of this relaxation remains incompletely understood. The present study aimed to investigate the effect of phytoestrogen genistein on the tension of rabbit femoral arteries in vitro and to determine the mechanism of such relaxation. The results are as follows: (1) Genistein (10 ~ 40 μmol/L) relaxed femoral arterial rings in a concentration-dependent manner under the condition of precontraction induced by phenylephrine (PE, 1μmol/L); (2) Removal of the endothelium significantly inhibited genistein-induced relaxation; (3) Pretreatment with NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) also significantly inhibited this relaxation by genistein, implying that the concentration-dependent vasorelaxation caused by genistein is endothelium-dependent and involved nitric oxide; (4) Pretreatment with an L-type calcium channel agonist, Bay K 8644 (0.5 μmol/L), also significantly inhibited the genistein-induced relaxation in both endothelium-intact and endothelium-denuded rings. The results suggest that the genistein-induced vascular relaxation of the rabbit arteries is partially endothelium-dependent and involves calcium antagonistic mechanism.2 Responses of regional vascular beds to local injection of genistein in rats The effects of local injection of genistein on femoral, renal, and mesenteric vascular beds were investigated respectively by constant flow perfusion method in 72 anaesthetized rats. The results are as follows: (1) Genistein (0.4, 0.8, 1.2 mg/kg) decreased the perfusion pressure (PP) of femoral vascular bed in a dose-dependent manner. The effect of genistein (0.8 mg/kg) was partially inhibited by L-NAME, or by sodium orthovanadate (50μg/kg), a potent inhibitor of protein...