Mechanisms of 17h-estradiol on the production of ET-1 in ovariectomized rats
Life Sciences 73(2003)2665-2674，-0001，（）：
In order to clarify the mechanism underlying the possible preventive effect of estrogen on atherogenesis, we investigated the role of 17h-estradiol (E2) in the regulation of endothelin-1 (ET-1) production in ovariectomized rats, which may contribute to atherogenesis. Female Spragure-Dawly rats were randomly divided into three groups: sham-operated group (sham), ovariectomized group (OVX) and 17h-estradiol replacement group (OVX +E2, 20μg-1.kg.d-1,s.c.). 4 weeks after operation, the plasma concentration of ET-1, clearance of ET-1, functional ECE activity and preproET-1 mRNA expression in aorta were measured. Concentration of plasma ET-1 change from 107.8±18.3pg/ml (sham)and 135.5±27.6pg/ml (OVX + E2) to 190.7±25.5μg/ml (OVX ) (n=8, p<0.05). There was no significant difference in the clearance of 125IET-1 among three groups (p>0.05). Functional ECE activity was increased in OVX group in comparison to that in sham group (p<0.05). The OVX increased the preproET-1 mRNA expression in sham, whereas treatment with estrogen reversed these changes (p<0.05). The present study have shown that estrogen down-regulates plasma ET-1 levels by inhibiting the preproET-1 mRNA expression and functional ECE activity. Clearance of ET-1 was not affected. Inhibition of ET-1 production mediated by modulating ECE activity may be one of the novel mechanisms of the protective of estrogens on the cardiovascular system. D 2003 Elsevier Inc. All rights reserved.
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