endothelin-1 and estradiol-dipropionate

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.

Topics: Animals; Aorta; DNA; Endothelin-1; Estradiol; Estrogens; Female; Femoral Artery; Gene Expression Regulation; Immunohistochemistry; Ovariectomy; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; RNA, Messenger