Preventive mechanism of genistein on coronary endothelial dysfunction in ovariectomized rats: an isolated arrested...

The effects of genistein on coronary endothelial dysfunction in bilateral ovariectomized rats were examined. Female Wistar rats were subjected to a bilateral ovariectomy (OVX rat). The animals were divided into three groups: sham treated with vehicle (DMSO 100 microl/day, Sham-DMSO), OVX treated with vehicle (DMSO 100 microl/day, OVX-DMSO), and OVX treated with genistein (0.25 mg/kgBW/day, OVX-genistein). Mean arterial pressure (MAP), heart rate (HR), body weight (BW), uterine weight and plasma E2 were monitored at 4- and 10-week after the treatment. We investigated the endothelium-dependent and -independent vasorelaxation by using acetylcholine (Ach 10(-5) M) and sodium nitroprusside (SNP 10(-7) M), respectively. The experimental results indicated that the uterine weights of all OVX rats were significantly decreased as compared to the sham groups. HR and MAP of both OVX-DMSO and OVX-genistein on 4 and 10 weeks were no significantly increased as compared to the Sham groups. The present coronary vasodilatation responses demonstrated only the significant decrement of endothelium-dependent, not for endothelium-independent, in OVX rats. The treatment of genistein could significantly attenuate this abnormality (% changes of vessel diameter obtained after Ach 10(-6) M: Sham-DMSO(10-wk) = 10.96 +/- 1.2%, OVX-DMSO(10-wk) = 3.2 +/- 0.77%, OVX-genistein(10-wk) = 11.45 +/- 1.85%), (% changes of vessels diameter obtained after SNP 10(-7)M: Sham-DMSO(10-wk) = 16.05 +/- 2.82%, OVX-DMSO(10-wk) = 12.73 +/- 2.72%, OVX-genistein(10-wk) = 16.4 +/- 4.71%) (p < 0.05). However, the lipid profiles monitored from all groups of 4 and 10 weeks did not demonstrate any significant changes. Therefore, it implied that endothelial dysfunction was not primarily cause by the lipid profiles changing in ovariectomized rats. Moreover, such effects of estrogen lacking on coronary endothelial-dependent vasodilatation could be attenuated by genistein supplementation. The present findings suggest that genistein might be used as an therapeutic agent for preventing the menopausal vascular complications.