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

This study sought to evaluate whether the effects of acute and long‐term treatment with 17‐β‐estradiol on the vasomotor responses in rat aortic rings are mediated through the same mechanism. Ovariectomized rats were treated daily with either 17‐β‐estradiol‐3‐benzoate (100 μg kg −1 ) or vehicle for 1 week. The effect of long‐term 17‐β‐estradiol treatment on the responses to cumulative doses of phenylephrine, 5‐HT, calcium, potassium and 17‐β‐estradiol was determined in aortic rings. In the same rings, the effect of acute exposure to 17‐β‐estradiol (5 and 10 μ 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. Long‐term 17‐β‐estradiol treatment reduced the maximum developed contraction to all contracting agents studied. This effect was abolished in endothelium denuded vessels. Acute 17‐β‐estradiol treatment also reduced maximal contraction. This effect, however, was independent of the endothelium. Long‐term 17‐β‐estradiol treatment significantly increased the ability of the rings to dilate in response to acetylcholine whereas acute exposure to 17‐β‐estradiol had no effect. The tone‐related release of NO was significantly increased after long‐term exposure to 17‐β‐estradiol. In conclusion, this study indicate that the acute and long‐term effects of 17‐β‐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‐β‐estradiol seems to be through an effect on the vascular smooth muscle cells.British Journal of Pharmacology (1999) 126 , 159–168; doi: 10.1038/sj.bjp.0702289