January 1999, Volume 126, Issue 1, Pages 159 - 168

Original Article

Effect of acute and long-term treatment with 17--estradiol on the vasomotor responses in the rat aorta Heidi L. Andersen1,4, Jan U. Weis1, Bjarne Fjalland2 & Niels Korsgaard3 1Department of Preclinical Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark     2Department of Pharmacology, Royal Danish School of Pharmacy, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark     3Department of Histology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark     4Author for correspondence

Keywords

17--Estradiol;   acute;   aorta;   calcium;   long-term;   nitric oxide;   rat;   vasomotor response

Abstract

1   This study sought to evaluate whether the effects of acute and long-term treatment with 17--estradiol on the vasomotor responses in rat aortic rings are mediated through the same mechanism. 2   Ovariectomized rats were treated daily with either 17--estradiol-3-benzoate (100 µg kg-1) or vehicle for 1 week. 3   The effect of long-term 17--estradiol treatment on the responses to cumulative doses of phenylephrine, 5-HT, calcium, potassium and 17--estradiol was determined in aortic rings. In the same rings, the effect of acute exposure to 17--estradiol (5 and 10 µM) 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--estradiol treatment reduced the maximum developed contraction to all contracting agents studied. This effect was abolished in endothelium denuded vessels. Acute 17--estradiol treatment also reduced maximal contraction. This effect, however, was independent of the endothelium. 5   Long-term 17--estradiol treatment significantly increased the ability of the rings to dilate in response to acetylcholine whereas acute exposure to 17--estradiol had no effect. The tone-related release of NO was significantly increased after long-term exposure to 17--estradiol. 6   In conclusion, this study indicate that the acute and long-term effects of 17--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--estradiol seems to be through an effect on the vascular smooth muscle cells.

Received 18 May 1998; Revised 9 October 1998; Accepted 13 October 1998

^© Macmillan Publishers Ltd 1999