Effects If Estrogen On The Expression Of Artery Estrogen Receptor And The Activity Of Vascular Endothelial Nitric Oxide Synthase

Epidermiological investigations demonstrate that the cadiovascular mortality in postmenopausal women receving estrogen replacement therapy (ERT) is 30-50% less than that in their untreated countparts. However, the present therapeutic application of estrogens to treating heart disease is limited by the fact that the underlying protective mechanism is only partly understood. The benificial effect of estrogens on lipid metabolism and the formation of atherosclerosis plaque in arterial vessels have long been described, but the magnitude of these effects dose not frilly explain the protective action. Estrogen receptors (ER) exist in the blood vessel wall, a recent study has been reported the decrease or even absence of estrogen receptor in human atherosclerotic plaque, suggesting estrogen receptor plays a functional role in coronary atheroprotection. Whereas the effects of menopause and hormone replacement therapy (HRT) on the number of artery ER and its?role in the cardiovascular proection of estrogen have not been described. Nitric oxide (NO) is a kind of endothelium-derived relaxing factors and possesses many antiatherogenic properties. Literature has been shown that aorta of female rabbits releases a greater amount of NO than that of ovariectomized females as well as that of males. The findings suggest that NOS may be regulated by sex hormone and it is possible that the mechanism of estrogen induced vasodilation and protection against atherosclerosis is partly mediated by NO. Based on the viewpoint mentioned above, we investigated the effects of ovariectomy and hormone replacment therapy on the number of artery ER in female rat, and also observed whether estrogen had detectable effects on eNOS activity and NO release of endothelial cells. Methods: 1. Forty female rats were randomly divided into four groups: group A: Shamoperation; group B: Ovariectomy; group C: Ovariectomy with estrogen replacement therapy; group D: Ovariectomy with estrogen and progesteron replacement therapy. The rats were given normal diet and killed two month later, the receptor binding assay was adopted to measure the number of estrogen receptors in the artery of the rat. 2. Rat lung vascular endothelial cells (EC) were cultured according to the blocks explanting method and propagated in phenol-red free 1640 medium. The cells were treated with several different concentrations of 17 ~ 梕stradiol (with or without progesteron, L-Arg, L-NNA or estrogen receptor antagonist tamoxifen (lnmol/L). The production of nitric oxide was assessed by Griess reaction and the activity of NOS was assessed by Hemoglobin Reductase. The receptor binding assay (RBA) was adopted to measure the estrogen receptors in the endothelial cells. Results 1. RBA showed the existence of estrogen receptors in the artery and vascular endothelial cells of adult female rat; 2. The number of ER in the artery of group B is less than that in group A (P<0.05); 3. The number of ER in the arteries of group C and D are higher than that in group B (PK0.05), while there were no differences in the number of ER between group C and D (P>0.05). No significant differences were observed in the Kd value among the four groups (P>0.05); 4. Treatment with 17 f3 stradiol over 8 hour to 24 hours significantly enhanced the production of NO (lnmoIIL, l0nmol/L E2 vs control, P<0.05) and the activity of...