Effect of acute and long-term treatment with 17-β-estradiol on the vasomotor responses in the rat aorta

被引:62
作者
Andersen, HL
Weis, JU
Fjalland, B
Korsgaard, N
机构
[1] Novo Nordisk AS, Dept Preclin Pharmacol, DK-2760 Malov, Denmark
[2] Novo Nordisk AS, Royal Danish Sch Pharm, Dept Pharmacol, DK-2760 Malov, Denmark
[3] Novo Nordisk AS, Dept Histol, DK-2760 Malov, Denmark
关键词
17-beta-estradiol; acute; aorta; calcium; long-term; nitric oxide; rat; vasomotor response;
D O I
10.1038/sj.bjp.0702289
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 This study sought to evaluate whether the effects of acute and long-term treatment with 17-beta-estradiol on the vasomotor responses in rat aortic rings are mediated through the same mechanism. 2 Ovariectomized rats were treated daily with either 17-beta-estradiol-3-benzoate (100 mu g kg(-1)) or vehicle for 1 week. 3 The effect of long-term 17-beta-estradiol treatment on the responses to cumulative doses of phenylephrine, 5-HT, calcium, potassium and 17-beta-estradiol was determined in aortic rings. In the same rings, the effect of acute exposure to 17-beta-estradiol (5 and 10 mu M) on the dose response curves for phenylephrine, 5-HT, calcium, potassium and acetylcholine were estimated. The measurements were made in rings with and without intact endothelium. The tone-related basal release of nitric oxide (NO) was measured in rings with intact endothelium. 4 Long-term 17-beta-estradiol treatment reduced the maximum developed contraction to all contracting agents studied. This effect was abolished in endothelium denuded vessels. Acute 17-beta-estradiol treatment also reduced maximal contraction. This effect, however, was independent of the endothelium. 5 Long-term 17-beta-estradiol treatment significantly increased the ability of the rings to dilate in response to acetylcholine whereas acute exposure to 17-beta-estradiol had no effect. The tone-related release of NO was significantly increased after long-term exposure to 17-beta-estradiol. 6 In conclusion, this study indicate that the acute and long-term effects of 17-beta-estradiol in the rat aorta are mediated through different mechanisms. The long-term effect is mediated through the endothelium most likely by increasing NO release. In contrast, the acute effect of 17-beta-estradiol seems to be through an effect on the vascular smooth muscle cells.
引用
收藏
页码:159 / 168
页数:10
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