Author/Authors :
Masahiro Akishita، نويسنده , , Yasuyoshi Ouchi، نويسنده , , Hideyuki Miyoshi، نويسنده , , Akira Orimo، نويسنده , , Koichi Kozaki، نويسنده , , Masato Eto، نويسنده , , Michiro Ishikawa، نويسنده , , Seungbum Kim، نويسنده , , Kenji Toba، نويسنده , , Hajime Orimo، نويسنده ,
Abstract :
In order to clarify the mechanism underlying the preventive effect of estrogen on atherogenesis, we investigated the role of estrogen in the regulation of endothelin-1 (ET-1) production and c-fos mRNA expression, which may contribute to atherogenesis. Plasma ET-1 concentration in ovariectomized rats (OVX) was twice as high as that in sham-operated female rats (Sham). Estradiol replacement in OVX rats (OVX + E) decreased plasma ET-1 to the level in Sham (Sham, 0.68 ± 0.14; OVX, 1.32 ± 0.14; OVX + E, 0.85 ± 0.12 pg/ml). Metabolic clearance rate of ET-1 was similar in these three groups of rats, suggesting that the difference in plasma ET-1 was due to production rather than degradation. Measurement of immunoreactive ET-1 in tissue extract and immunohistochemical examination showed that expression of ET-1 in the aortic smooth muscle cells of OVX was increased. The expression of c-fos mRNA in the aorta was also increased in OVX compared with Sham and OVX + E. Intravenous infusion of ET-1 to Sham induced c-fos expression in the aorta, suggesting the contribution of ET-1 to c-fos expression. Tissue culture study revealed that DNA synthesis was increased in the aorta and femoral artery of OVX. These results suggest that inhibition of ET-1 and c-fos expression is involved in the anti-atherogenic action of estrogen.
