Genistein replacement therapy for vasodilation disorder in bilateral ovariectomized rats

Abstract

The objective of this study is to examine the effects of genistein on endothelial dysfunction in bilateral ovariectomized rats. Female Wistar rats were subjected to a bilateral ovariectomy (OVX rat). The animals were divided into three groups: sham treated with vehicle (DMSO 100 μl/day, Sham_veh), OVX treated with vehicle (DMSO 100 μl/day, OVX_veh), and OVX treated with genistein (0.25 mg/kg BW/day, OVX_gen). Mean arterial pressure (MAP), heart rate (HR), body weight (BW), uterine weight and plasma E₂ were monitored at 4‐week after the treatment. We investigated the endothelium‐dependent and ‐independent vasorelaxation by using acetylcholine (Ach 10⁻⁶ 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 (OVX $\tsub{veh}=0.007\pm 0.004$ g, OVX $\tsub{gen}=0.003\pm 0.001$ g, Sham $\tsub{veh}=0.017\pm 0.001$ g). MAP of OVX_veh group was significantly increased compared to the Sham group (OVX $\tsub{veh}=139.99\pm 7.50$ mmHg, Sham $\tsub{veh}=118.10\pm19.33$ mmHg, p<0.05). No significant increase in MAP was observed in OVX_gen (OVX $\tsub{gen}=123.33\pm 8.61$ mmHg; p<0.05). HR showed no significant difference among those groups. The present study of vasodilator responses demonstrated only the significant decrease in endothelium‐dependent, not for endothelium‐independence, in OVX rats, while the treatment of genistein could significantly attenuate this abnormality (OVX $\tsub{veh}=3.03\pm3.99$ %, Sham $\tsub{veh}=45.46\pm 3.59$ %, OVX $\tsub{gen}=33.52\pm 3.25$ % in % change of vessel diameter). The present findings suggest that genistein could be used as a therapeutic agent for menopausal vascular complications.